endopeptidase clp

Summary

Summary: An ATP-dependent protease found in prokaryotes, CHLOROPLASTS, and MITOCHONDRIA. It is a soluble multisubunit complex that plays a role in the degradation of many abnormal proteins.

Top Publications

  1. ncbi Adapting the machine: adaptor proteins for Hsp100/Clp and AAA+ proteases
    Janine Kirstein
    Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2005 Tech Drive Hogan 2 100 Evanston, IL 60208, USA
    Nat Rev Microbiol 7:589-99. 2009
  2. pmc Structures of asymmetric ClpX hexamers reveal nucleotide-dependent motions in a AAA+ protein-unfolding machine
    Steven E Glynn
    Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 139:744-56. 2009
  3. pmc Single-molecule protein unfolding and translocation by an ATP-fueled proteolytic machine
    Marie Eve Aubin-Tam
    Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 145:257-67. 2011
  4. ncbi ClpP is involved in the stress response and degradation of misfolded proteins in Salmonella enterica serovar Typhimurium
    L E Thomsen
    Department of Veterinary Microbiology, Stigboejlen 4, The Royal Veterinary and Agricultural University, DK 1870 Frederiksberg C, Denmark
    Microbiology 148:2727-33. 2002
  5. pmc ClpXP, an ATP-powered unfolding and protein-degradation machine
    Tania A Baker
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Biochim Biophys Acta 1823:15-28. 2012
  6. pmc The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system
    S Gottesman
    Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892, USA
    Genes Dev 12:1338-47. 1998
  7. ncbi Engineering controllable protein degradation
    Kathleen E McGinness
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Mol Cell 22:701-7. 2006
  8. ncbi Dynamics of substrate denaturation and translocation by the ClpXP degradation machine
    Y I Kim
    Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139, USA
    Mol Cell 5:639-48. 2000
  9. ncbi Multiple pathways for regulation of sigmaS (RpoS) stability in Escherichia coli via the action of multiple anti-adaptors
    Alexandre Bougdour
    Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Microbiol 68:298-313. 2008
  10. ncbi The ClpX chaperone modulates assembly of the tubulin-like protein FtsZ
    Richard B Weart
    Department of Biology, Washington University, St Louis, MO 63130, USA
    Mol Microbiol 57:238-49. 2005

Research Grants

  1. Energy Landscapes for Acetylcholine Receptor Gating
    Stuart Licht; Fiscal Year: 2002
  2. Bacterial Response to Singlet Oxygen
    Timothy Donohue; Fiscal Year: 2009
  3. mazEF-mediated programmed cell death network in E. coli
    Hanna Engelberg Kulka; Fiscal Year: 2010
  4. Rat, a regulator of autolysis in S. aureus
    Ambrose Cheung; Fiscal Year: 2008
  5. Binding and regulation mechanism for S aureus
    Ambrose Cheung; Fiscal Year: 2006
  6. IN VIVO GENE EXPRESSION IN STAPHYLOCCUS AUREUS
    Ambrose Cheung; Fiscal Year: 2009

Detail Information

Publications192 found, 100 shown here

  1. ncbi Adapting the machine: adaptor proteins for Hsp100/Clp and AAA+ proteases
    Janine Kirstein
    Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2005 Tech Drive Hogan 2 100 Evanston, IL 60208, USA
    Nat Rev Microbiol 7:589-99. 2009
    ..Here, we review our current knowledge of the modulation of bacterial AAA+ proteases by these cellular arbitrators...
  2. pmc Structures of asymmetric ClpX hexamers reveal nucleotide-dependent motions in a AAA+ protein-unfolding machine
    Steven E Glynn
    Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 139:744-56. 2009
    ....
  3. pmc Single-molecule protein unfolding and translocation by an ATP-fueled proteolytic machine
    Marie Eve Aubin-Tam
    Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 145:257-67. 2011
    ..We anticipate that single-molecule studies of the mechanical properties of other AAA+ proteolytic machines will reveal many shared features with ClpXP...
  4. ncbi ClpP is involved in the stress response and degradation of misfolded proteins in Salmonella enterica serovar Typhimurium
    L E Thomsen
    Department of Veterinary Microbiology, Stigboejlen 4, The Royal Veterinary and Agricultural University, DK 1870 Frederiksberg C, Denmark
    Microbiology 148:2727-33. 2002
    ..typhimurium clpP mutant is generally more sensitive to environmental stress than the E. coli clpP mutant and it is proposed that this is due to a reduced ability to degrade misfolded proteins generated under these conditions...
  5. pmc ClpXP, an ATP-powered unfolding and protein-degradation machine
    Tania A Baker
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Biochim Biophys Acta 1823:15-28. 2012
    ..Here, we review our present understanding of ClpXP structure and function, as revealed by two decades of biochemical and biophysical studies...
  6. pmc The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system
    S Gottesman
    Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892, USA
    Genes Dev 12:1338-47. 1998
    ....
  7. ncbi Engineering controllable protein degradation
    Kathleen E McGinness
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Mol Cell 22:701-7. 2006
    ....
  8. ncbi Dynamics of substrate denaturation and translocation by the ClpXP degradation machine
    Y I Kim
    Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139, USA
    Mol Cell 5:639-48. 2000
    ..These insights into the mechanism of ClpXP explain how it executes efficient degradation in a manner that is highly specific for tagged proteins, irrespective of their intrinsic stabilities...
  9. ncbi Multiple pathways for regulation of sigmaS (RpoS) stability in Escherichia coli via the action of multiple anti-adaptors
    Alexandre Bougdour
    Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Microbiol 68:298-313. 2008
    ..Our results reveal that multiple anti-adaptor proteins allow the regulation of sigmaS stability through the regulation of RssB activity under a variety of stress conditions...
  10. ncbi The ClpX chaperone modulates assembly of the tubulin-like protein FtsZ
    Richard B Weart
    Department of Biology, Washington University, St Louis, MO 63130, USA
    Mol Microbiol 57:238-49. 2005
    ..ClpX is conserved throughout bacteria and has been shown to interact directly with FtsZ in Escherichia coli. Thus, we speculate that ClpX functions as a general regulator of FtsZ assembly and cell division in a wide variety of bacteria...
  11. pmc Global regulatory impact of ClpP protease of Staphylococcus aureus on regulons involved in virulence, oxidative stress response, autolysis, and DNA repair
    Antje Michel
    Institut für Molekulare Infektionsbiologie, Rontgenring 11, D 97070 Wurzburg, Germany
    J Bacteriol 188:5783-96. 2006
    ..Our results indicate a strong impact of ClpP proteolytic activity on virulence, stress response, and physiology in S. aureus...
  12. ncbi The ATP-dependent ClpXP and Lon proteases regulate expression of the Yersinia pestis type III secretion system via regulated proteolysis of YmoA, a small histone-like protein
    Michael W Jackson
    Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33136, USA
    Mol Microbiol 54:1364-78. 2004
    ..These results indicate that the ClpXP and Lon proteases contribute to the environmental regulation of the Y. pestis T3SS system through regulated proteolysis of YmoA...
  13. ncbi Role of the GYVG pore motif of HslU ATPase in protein unfolding and translocation for degradation by HslV peptidase
    Eunyong Park
    NRL of Protein Biochemistry, School of Biological Sciences, Seoul National University, Korea
    J Biol Chem 280:22892-8. 2005
    ..These results also implicate a role of the pore motif in ATP cleavage and in the assembly of HslVU complex...
  14. pmc A peptide signal for adapter protein-mediated degradation by the AAA+ protease ClpCP
    Peter Prepiak
    Public Health Research Institute, 225 Warren Street, Newark, NJ 07103, USA
    Mol Cell 26:639-47. 2007
    ..We propose a model in which the antiadaptor protein ComS acts by direct competition to protect ComK from degradation...
  15. pmc Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine
    Steven E Glynn
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    Nat Struct Mol Biol 19:616-22. 2012
    ....
  16. ncbi Mcx1p, a ClpX homologue in mitochondria of Saccharomyces cerevisiae
    L van Dyck
    Institut für Physiologische Chemie der Universität München, Munich, Germany
    FEBS Lett 438:250-4. 1998
    ..A homologue of E. coli ClpP protease was not identified when screening the yeast genome. We therefore propose that Mcx1p represents a novel molecular chaperone of mitochondria with non-proteolytic function...
  17. pmc Cross genome comparisons of serine proteases in Arabidopsis and rice
    Lokesh P Tripathi
    National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK Campus, Bellary Road, Bangalore 560 065, India
    BMC Genomics 7:200. 2006
    ..The availability of Arabidopsis thaliana and rice (Oryza sativa) genome sequences has permitted the identification and comparison of the repertoire of serine protease-like proteins in the two plant species...
  18. ncbi Structure and mechanism of the hexameric MecA-ClpC molecular machine
    Feng Wang
    Center for Structural Biology, School of Life Sciences and School of Medicine, Tsinghua University, Beijing 100084, China
    Nature 471:331-5. 2011
    ..These findings have implications for related Clp/Hsp100 molecular machines...
  19. ncbi The ClpP serine protease is essential for the intracellular parasitism and virulence of Listeria monocytogenes
    O Gaillot
    INSERM U411, Centre Hospitalo Universitaire Necker Enfants Malades, 156, rue de Vaugirard, 75730 Paris Cedex 15, France
    Mol Microbiol 35:1286-94. 2000
    ..These results suggest that ClpP is involved in the rapid adaptive response of intracellular pathogens during the infectious process...
  20. pmc Decline in ribosomal fidelity contributes to the accumulation and stabilization of the master stress response regulator sigmaS upon carbon starvation
    Asa Fredriksson
    Department of Cell and Molecular Biology Microbiology, Goteborg University, 405 30 Goteborg, Sweden
    Genes Dev 21:862-74. 2007
    ..We present a model for the sequence of events leading to the accumulation and activation of sigma(S) upon carbon starvation, which are linked to alterations in both ribosomal fidelity and efficiency...
  21. pmc Controlled degradation by ClpXP protease tunes the levels of the excision repair protein UvrA to the extent of DNA damage
    Mihaela Pruteanu
    Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Microbiol 71:912-24. 2009
    ....
  22. pmc Lon and Clp family proteases and chaperones share homologous substrate-recognition domains
    C K Smith
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 96:6678-82. 1999
    ....
  23. pmc Clp-dependent proteolysis down-regulates central metabolic pathways in glucose-starved Bacillus subtilis
    Ulf Gerth
    Ernst Moritz Arndt University, Institute of Microbiology, F L Jahn Str 15, D 17487 Greifswald, Germany
    J Bacteriol 190:321-31. 2008
    ..Proteins that are obviously nonfunctional, unprotected, or even "unemployed" seem to be recognized and proteolyzed by Clp proteases when the resources for growth become limited...
  24. pmc The ClpXP ATP-dependent protease regulates flagellum synthesis in Salmonella enterica serovar typhimurium
    Toshifumi Tomoyasu
    Department of Microbiology and Molecular Genetics, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263 8522, Japan
    J Bacteriol 184:645-53. 2002
    ....
  25. ncbi The gene complement for proteolysis in the cyanobacterium Synechocystis sp. PCC 6803 and Arabidopsis thaliana chloroplasts
    Anna Sokolenko
    Department I, Bereich Botanik, Ludwig Maximilians Universitat, Menzingerstrasse 67, 80638 Munchen, Germany
    Curr Genet 41:291-310. 2002
    ..This reorganization in the pattern of proteolytic enzymes may reflect distinct environmental and physiological changes between prokaryotic and organellar systems...
  26. pmc Pore loops of the AAA+ ClpX machine grip substrates to drive translocation and unfolding
    Andreas Martin
    Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Nat Struct Mol Biol 15:1147-51. 2008
    ..These results support a model in which nucleotide-dependent conformational changes in these pore loops drive substrate translocation and unfolding, with the aromatic ring transmitting force to the polypeptide substrate...
  27. ncbi Beta-lactones as specific inhibitors of ClpP attenuate the production of extracellular virulence factors of Staphylococcus aureus
    Thomas Böttcher
    Center for integrated Protein Science Munich CIPS M, Department of Chemistry and Biochemistry, Ludwig Maximilians Universitat Munchen, Butenandtstrasse 5 13, 81377 Munich, Germany
    J Am Chem Soc 130:14400-1. 2008
    ....
  28. pmc Regulation and Physiological Significance of ClpC and ClpP in Streptococcus mutans
    José A C Lemos
    Department of Oral Biology, College of Dentistry, University of Florida, Gainesville 32610, USA
    J Bacteriol 184:6357-66. 2002
    ..In particular, in the clpP mutant, there was an increased production of GroESL and DnaK, suggesting that cells were stressed, probably due to the accumulation of denatured proteins...
  29. ncbi Functional proteolytic complexes of the human mitochondrial ATP-dependent protease, hClpXP
    Sung Gyun Kang
    Laboratory of Cell Biology, NCI and Laboratory of Structural Biology, NIAMS, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 277:21095-102. 2002
    ..Our data also indicate that human ClpP has conserved sites required for interaction with eClpX but not eClpA, implying that the modes of interaction with ClpP may not be identical for ClpA and ClpX...
  30. ncbi Role of inorganic polyphosphate in promoting ribosomal protein degradation by the Lon protease in E. coli
    A Kuroda
    Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, 1 4 1 Kagamiyama, Hiroshima 739 8527, Japan
    Science 293:705-8. 2001
    ..Purified S2 also bound to polyP and formed a complex with Lon in the presence of polyP. Thus, polyP may promote ribosomal protein degradation by the Lon protease, thereby supplying the amino acids needed to respond to starvation...
  31. ncbi Alternative roles of ClpX and ClpP in Staphylococcus aureus stress tolerance and virulence
    Dorte Frees
    Department of Veterinary Microbiology, Royal Veterinary and Agricultural University KVL, Stigbøjlen 4, DK 1870 Frederiksberg C, Denmark
    Mol Microbiol 48:1565-78. 2003
    ..Thus, our results indicate that ClpX and ClpP contribute to virulence by controlling the activity of major virulence factors rather than by promoting stress tolerance...
  32. pmc Clp-mediated proteolysis in Gram-positive bacteria is autoregulated by the stability of a repressor
    E Kruger
    Institut fur Biochemie, Humboldt Universitat, Universitatsklinikum Charite, Monbijoustrasse 2, D 10117 Berlin, Germany
    EMBO J 20:852-63. 2001
    ..Thereby, the ClpC ATPase, a member of the Hsp100 family, was identified as a positive regulator of the heat shock response...
  33. pmc The ClpP peptidase is the major determinant of bulk protein turnover in Bacillus subtilis
    Holger Kock
    Ernst Moritz Arndt Universitat, Institut fur Mikrobiologie, F L Jahn Str 15, 17487 Greifswald, Germany
    J Bacteriol 186:5856-64. 2004
    ....
  34. ncbi Heat and DNA damage induction of the LexA-like regulator HdiR from Lactococcus lactis is mediated by RecA and ClpP
    Kirsi Savijoki
    University of Helsinki, Faculty of Veterinary Medicine, Department of Basic Veterinary Sciences, Division of Microbiology and Epidemiology, PO Box 57, 00014 Helsinki University, Helsinki, Finland
    Mol Microbiol 50:609-21. 2003
    ..Thus, our data show that common elements are involved in both the DNA damage and the heat-mediated induction of the HdiR regulon...
  35. pmc Role of the processing pore of the ClpX AAA+ ATPase in the recognition and engagement of specific protein substrates
    Samia M Siddiqui
    Massachusetts Institute of Technology, Department of Biology, Howard Hughes Medical Institute, Cambridge, Massachusetts 02139, USA
    Genes Dev 18:369-74. 2004
    ..These results demonstrate that the ClpX pore functions in the recognition and catalytic engagement of specific substrates, and that ClpX recognizes different substrate classes in at least two distinct fashions...
  36. ncbi Protein unfolding by a AAA+ protease is dependent on ATP-hydrolysis rates and substrate energy landscapes
    Andreas Martin
    Department of Biology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Nat Struct Mol Biol 15:139-45. 2008
    ..We propose that cellular conditions or adaptors that alter ATP-hydrolysis rates could control this trapping activity of AAA+ enzymes...
  37. ncbi Helicobacter pylori mutants defective in the clpP ATP-dependant protease and the chaperone clpA display reduced macrophage and murine survival
    Michael F Loughlin
    Institute of Infection, Immunity and Inflammation, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2UH, UK
    Microb Pathog 46:53-7. 2009
    ..In the mouse infection model the double mutant SS1 clpAP lacked all ability to colonize the murine host. This suggests that the ability to recover from protein damage is of key importance in the pathogenesis of this organism...
  38. ncbi The ClpPX protease is required for radioresistance and regulates cell division after gamma-irradiation in Deinococcus radiodurans
    Pascale Servant
    Universite Paris Sud 11, CNRS UMR 8621, LRC CEA 42V, Institut de Genetique et Microbiologie, Batiment 409, F 91405 Orsay cedex, France
    Mol Microbiol 66:1231-9. 2007
    ..We propose that the ClpPX protease is involved in the control of proper chromosome segregation and cell division in cells recovering from DNA damage...
  39. pmc The replication initiation protein of the broad-host-range plasmid RK2 is activated by the ClpX chaperone
    I Konieczny
    Department of Biology, Center for Molecular Genetics, University of California, San Diego, La Jolla, CA 92093 0634, USA
    Proc Natl Acad Sci U S A 94:14378-82. 1997
    ..Finally, a copy-up mutant of the TrfA protein which is largely in the monomer form is active in the reconstituted in vitro replication system, and its activity is not affected by ClpX...
  40. pmc Conformation of a plasmid replication initiator protein affects its proteolysis by ClpXP system
    Marcin Pierechod
    Department of Molecular and Cellular Biology, Faculty of Biotechnology, University of Gdansk, Gdansk, Poland
    Protein Sci 18:637-49. 2009
    ..Our data also show that the plasmid replication initiator activity and stability in E. coli cells are affected by ClpXP system only when the protein sustains dimeric form...
  41. ncbi Crystal structure of ClpX molecular chaperone from Helicobacter pylori
    Dong Young Kim
    Department of Molecular Cell Biology, Center for Molecular Medicine, SBRI, Sungkyunkwan University School of Medicine, Suwon 440 746, Korea
    J Biol Chem 278:50664-70. 2003
    ..In addition, the nucleotide binding environment provides the structural explanation for the hexameric assembly and the modulation of ATPase activity...
  42. pmc Formation of the preprimosome protects lambda O from RNA transcription-dependent proteolysis by ClpP/ClpX
    M Zylicz
    Department of Molecular and Cellular Biology, Faculty of Biotechnology, University of Gdansk, 80 822 Gdansk, Kladki 24, Poland
    Proc Natl Acad Sci U S A 95:15259-63. 1998
    ..These results show that transcription can stimulate proteolysis of a protein that is required for the initiation of DNA replication...
  43. pmc Stepwise unfolding of a β barrel protein by the AAA+ ClpXP protease
    Andrew R Nager
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Mol Biol 413:4-16. 2011
    ..Our results suggest that the presence or absence of unfolding intermediates will play important roles in determining whether forced enzymatic unfolding requires a minimum rate of ATP hydrolysis...
  44. ncbi The DnaK-DnaJ-GrpE chaperone system activates inert wild type pi initiator protein of R6K into a form active in replication initiation
    Shamsu Zzaman
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    J Biol Chem 279:50886-94. 2004
    ....
  45. ncbi Maintenance of mitochondrial genome distribution by mitochondrial AAA+ protein ClpX
    Katsumi Kasashima
    Jichi Medical University, Department of Biochemistry, Tochigi 329 0498, Japan
    Exp Cell Res 318:2335-43. 2012
    ..These results suggest that human ClpX, a novel mtDNA regulator, maintains mtDNA nucleoid distribution through TFAM function as a chaperone rather than as a protease and its involvement in mtDNA segregation...
  46. ncbi Asymmetric interactions of ATP with the AAA+ ClpX6 unfoldase: allosteric control of a protein machine
    Greg L Hersch
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02319, USA
    Cell 121:1017-27. 2005
    ..These studies further emphasize commonalities between distant AAA+ family members, including protein and DNA translocases, helicases, motor proteins, clamp loaders, and other ATP-dependent enzymes...
  47. ncbi Crystal structure of ClpA, an Hsp100 chaperone and regulator of ClpAP protease
    Fusheng Guo
    Laboratory of Cell Biology, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 277:46743-52. 2002
    ....
  48. ncbi Linkage between ATP consumption and mechanical unfolding during the protein processing reactions of an AAA+ degradation machine
    Jon A Kenniston
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Cell 114:511-20. 2003
    ..The ability to denature more stable proteins simply by using more ATP endows ClpX with a robust unfolding activity required for its biological roles in degradation and complex disassembly...
  49. pmc Localization of general and regulatory proteolysis in Bacillus subtilis cells
    Janine Kirstein
    Institut für Biologie Mikrobiologie, FU Berlin, Berlin, Germany
    Mol Microbiol 70:682-94. 2008
    ....
  50. pmc Regulation of Escherichia coli starvation sigma factor (sigma s) by ClpXP protease
    T Schweder
    Department of Microbiology and Immunology, Stanford University, School of Medicine, California 94305 5402, USA
    J Bacteriol 178:470-6. 1996
    ..Studies with translational fusions containing different lengths of sigma s coding region suggest that amino acid residues 173 to 188 of this sigma factor may directly or indirectly serve as at least part of the target for ClpXP protease...
  51. pmc Redundant in vivo proteolytic activities of Escherichia coli Lon and the ClpYQ (HslUV) protease
    W F Wu
    Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892 4255, USA
    J Bacteriol 181:3681-7. 1999
    ..Thus, a protease with a structure and an active site different from those of Lon is capable of recognizing and degrading two different Lon substrates and appears to act as a backup for Lon under certain conditions...
  52. pmc Clp and Lon proteases occupy distinct subcellular positions in Bacillus subtilis
    Lyle A Simmons
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    J Bacteriol 190:6758-68. 2008
    ..subtilis several ATP-fueled proteases occupy distinct subcellular locations. With these data, we suggest that substrate specificity could be determined, in part, by the spatial and temporal organization of proteases in vivo...
  53. pmc The AAA+ ClpX machine unfolds a keystone subunit to remodel the Mu transpososome
    Aliaa H Abdelhakim
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 107:2437-42. 2010
    ..The specific targeting of a stabilizing "keystone subunit" within a complex for unfolding is an attractive general mechanism for remodeling by AAA+ enzymes...
  54. pmc ClpAP and ClpXP degrade proteins with tags located in the interior of the primary sequence
    Joel R Hoskins
    Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 99:11037-42. 2002
    ..We also found that ClpA recognizes the NH2-terminal 15 aa RepA tag, when it is fused to the COOH terminus of GFP. Moreover, ClpA recognizes the RepA tag in either the authentic or inverse orientation...
  55. pmc Global transcriptional analysis of clpP mutations of type 2 Streptococcus pneumoniae and their effects on physiology and virulence
    Gregory T Robertson
    Infectious Diseases Research, Lilly Research Laboratories, Indianapolis, Indiana 46285, USA
    J Bacteriol 184:3508-20. 2002
    ..Together, these results indicate that ClpP-mediated proteolysis plays a complex and central role in numerous pneumococcal stress responses, development of competence, and virulence...
  56. ncbi ClpA and ClpP remain associated during multiple rounds of ATP-dependent protein degradation by ClpAP protease
    S K Singh
    Laboratory of Cell Biology, National Cancer Institute, Bethesda, Maryland 20892, USA
    Biochemistry 38:14906-15. 1999
    ..Our results indicate that the ClpAP complex is the functional form of the protease and as such engages in multiple rounds of interaction with substrate proteins, degradation, and release of peptide products without dissociation...
  57. ncbi ClpS, a substrate modulator of the ClpAP machine
    David A Dougan
    Institut fur Biochemie und Molekularbiologie, Universitat Freiburg, Hermann Herder Strasse 7, D 79104 Freiburg, Germany
    Mol Cell 9:673-83. 2002
    ..We conclude that ClpS modifies ClpA substrate specificity, potentially redirecting degradation by ClpAP toward aggregated proteins...
  58. ncbi Role of lon and ClpX in the post-translational regulation of a sigma subunit of RNA polymerase required for cellular differentiation in Bacillus subtilis
    J Liu
    Department of Biochemistry and Molecular Biology, Oregon Graduate Institute of Science and Technology, Portland, OR 97291 1000, USA
    Mol Microbiol 33:415-28. 1999
    ....
  59. ncbi Communication between ClpX and ClpP during substrate processing and degradation
    Shilpa A Joshi
    Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
    Nat Struct Mol Biol 11:404-11. 2004
    ..A simple model explains the observed relationships between ATP binding, ATP hydrolysis and functional interactions between ClpX, protein substrates and ClpP...
  60. pmc Identification of a bacterial-like HslVU protease in the mitochondria of Trypanosoma brucei and its role in mitochondrial DNA replication
    Ziyin Li
    Department of Pharmaceutical Chemistry, University of California, San Francisco, California, United States of America
    PLoS Pathog 4:e1000048. 2008
    ..TbHslVU is a eubacterial protease identified in the mitochondria of a eukaryote. It has a novel function in regulating mitochondrial DNA replication that has never been observed in other organisms...
  61. pmc Diverse pore loops of the AAA+ ClpX machine mediate unassisted and adaptor-dependent recognition of ssrA-tagged substrates
    Andreas Martin
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Cell 29:441-50. 2008
    ..This mechanism of initial tag binding would allow ATP-dependent conformational changes in one or more pore loops to drive peptide translocation, force unfolding, and mediate threading of the denatured protein through the ClpX pore...
  62. ncbi Functional domains of the ClpA and ClpX molecular chaperones identified by limited proteolysis and deletion analysis
    S K Singh
    Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 276:29420-9. 2001
    ....
  63. ncbi The ClpP double ring tetradecameric protease exhibits plastic ring-ring interactions, and the N termini of its subunits form flexible loops that are essential for ClpXP and ClpAP complex formation
    Anna Gribun
    Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    J Biol Chem 280:16185-96. 2005
    ..Mutation of several amino acid residues in this loop or the truncation of the loop impairs ClpXP and ClpAP complex formation and prevents the coupling between ClpX/ClpA and ClpP activities...
  64. pmc Distinct static and dynamic interactions control ATPase-peptidase communication in a AAA+ protease
    Andreas Martin
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Mol Cell 27:41-52. 2007
    ..Thus, discrete static and dynamic interactions mediate binding and communication between ClpX and ClpP...
  65. ncbi ClpS is an essential component of the N-end rule pathway in Escherichia coli
    A Erbse
    Zentrum für Molekulare Biologie Heidelberg, Universitat Heidelberg, INF 282, Heidelberg D 69120, Germany
    Nature 439:753-6. 2006
    ..Through interaction with this signal, ClpS converts the ClpAP machine into a protease with exquisitely defined specificity, ideally suited to regulatory proteolysis...
  66. pmc Regulation of SOS mutagenesis by proteolysis
    E G Frank
    Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 2725, USA
    Proc Natl Acad Sci U S A 93:10291-6. 1996
    ....
  67. ncbi Regulation by proteolysis in bacterial cells
    Urs Jenal
    Division of Molecular Microbiology, Biozentrum, Universitat Basel, Klingelbergstrasse 50 70, 4056 Basel, Switzerland
    Curr Opin Microbiol 6:163-72. 2003
    ..This information includes temporal and spatial cues, and recent research has revealed a striking potential for multiple signal integration...
  68. pmc ClpXP protease regulates the signal peptide cleavage of secretory preproteins in Bacillus subtilis with a mechanism distinct from that of the Ecs ABC transporter
    Tiina Pummi
    Vaccine Development Laboratory, National Public Health Institute, FIN 00300 Helsinki, Finland
    J Bacteriol 184:1010-8. 2002
    ..A concerted regulation of signal peptidase genes by a ClpXP-dependent activator is suggested. In contrast, Ecs did not affect transcription of the sip genes, pointing to a different mechanism of secretion regulation...
  69. ncbi Role of the Streptococcus agalactiae ClpP serine protease in heat-induced stress defence and growth arrest
    Shamila Nair
    INSERM U411, Faculte de Medecine Necker, 156 rue de Vaugirard, 75730 Paris Cedex 15, France
    Microbiology 149:407-17. 2003
    ..Even though ClpP plays a minor role in the virulence of S. agalactiae in a murine infection model, the data presented here point to the importance of ClpP in oxidative stress defence in preventing heat-induced cell alterations...
  70. ncbi AAA+ proteins and substrate recognition, it all depends on their partner in crime
    David A Dougan
    Zentrum für Molekulare Biologie Heidelberg, Universitat Heidelberg, Im Neuenheimer Feld 282, D 69120, Heidelberg, Germany
    FEBS Lett 529:6-10. 2002
    ....
  71. ncbi Proteolysis in prokaryotes: protein quality control and regulatory principles
    Regine Hengge
    Institut fur Biologie, Mikrobiologie, Freie Universitat Berlin, 14195 Berlin, Germany
    Mol Microbiol 49:1451-62. 2003
  72. ncbi Clp ATPases and ClpP proteolytic complexes regulate vital biological processes in low GC, Gram-positive bacteria
    Dorte Frees
    Department of Veterinary Pathobiology, Faculty of Life Sciences, University of Copenhagen, Stigbøjlen 4, DK 1870 Frederiksberg C, Denmark
    Mol Microbiol 63:1285-95. 2007
    ..Thus, Clp proteins are central in co-ordinating developmental decisions and stress response in low GC Gram-positive bacteria...
  73. ncbi Control of the endonuclease activity of type I restriction-modification systems is required to maintain chromosome integrity following homologous recombination
    Garry W Blakely
    Institute of Structural and Molecular Biology, University of Edinburgh, Edinburgh, Scotland, UK
    Mol Microbiol 60:883-93. 2006
    ..coli K-12. Previously, the potential of the second pathway has only been demonstrated when expression of lar has been elevated. Our data identify the effect of lar from the repressed prophage...
  74. ncbi ClpP: a distinctive family of cylindrical energy-dependent serine proteases
    Angela Yeou Hsiung Yu
    Department of Biochemistry, University of Toronto, Medical Sciences Building, 1 King s College Circle, Toronto, ON, Canada M5S 1A8
    FEBS Lett 581:3749-57. 2007
    ..Structural and functional studies have provided a detailed view of the mechanism of function of this class of proteases...
  75. ncbi A dynamically localized protease complex and a polar specificity factor control a cell cycle master regulator
    Patrick T McGrath
    Department of Physics, Stanford University, Stanford, CA 94305, USA
    Cell 124:535-47. 2006
    ..Thus, a dynamically localized ClpXP proteolysis complex in concert with a cytoplasmic factor provides temporal and spatial specificity to protein degradation during a bacterial cell cycle...
  76. ncbi Involvement of Clp protease activity in modulating the Bacillus subtilissigmaw stress response
    Stephan Zellmeier
    Institute of Genetics, University of Bayreuth, D 95440 Bayreuth, Germany
    Mol Microbiol 61:1569-82. 2006
    ....
  77. ncbi Bacterial inclusion bodies are cytotoxic in vivo in absence of functional chaperones DnaK or GroEL
    Nuria Gonzalez-Montalban
    Institut de Biotecnologia i de Biomedicina, Departament de Genetica i de Microbiologia, Universitat Autonoma de Barcelona, Bellaterra, 08193 Barcelona, Spain
    J Biotechnol 118:406-12. 2005
    ..The role of DnaK and GroEL in minimizing toxicity of in vivo protein aggregation is discussed in the context of the conformational stress and the protein quality control system...
  78. ncbi Role of ClpP in biofilm formation and virulence of Staphylococcus epidermidis
    Chongzhen Wang
    Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China
    Microbes Infect 9:1376-83. 2007
    ..Furthermore, clpP was found to be regulated by the quorum-sensing agr, suggesting that part of the previously described influence of agr on the initial attachment to plastic surfaces may be mediated by clpP...
  79. pmc Contribution of the ATP-dependent protease ClpCP to the autolysis and virulence of Streptococcus pneumoniae
    Yasser Musa Ibrahim
    Division of Infection and Immunity, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, United Kingdom
    Infect Immun 73:730-40. 2005
    ..We also report the requirement of ClpP for the growth at elevated temperature and virulence of serotype 4 strain TIGR4 and confirm its contribution to the thermotolerance, oxidative stress resistance, and virulence of D39...
  80. ncbi Clp ATPases are required for stress tolerance, intracellular replication and biofilm formation in Staphylococcus aureus
    Dorte Frees
    Department of Veterinary Pathobiology, Royal Veterinary and Agricultural University KVL, Stigbøjlen 4, DK 1870 Frederiksberg C, Denmark
    Mol Microbiol 54:1445-62. 2004
    ..Thus, our data show that Clp proteolytic complexes and the Clp ATPases control several key processes of importance to the success of S. aureus as a pathogen...
  81. ncbi Comparative genomics and functional roles of the ATP-dependent proteases Lon and Clp during cytosolic protein degradation
    Dilip Chandu
    Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India
    Res Microbiol 155:710-9. 2004
    ..Lon orthologs, unlike ClpP and ClpQ, are present in most organisms studied. The roles of these proteases as essential enzymes and in the virulence of some organisms are discussed...
  82. ncbi Assembly pathway of an AAA+ protein: tracking ClpA and ClpAP complex formation in real time
    Wolfgang Kress
    Institute of Molecular Biology and Biophysics, ETH Zurich, 8093 Zurich, Switzerland
    Biochemistry 46:6183-93. 2007
    ..The association of assembled ClpA hexamers with the ClpP core cylinder displays cooperativity, supporting the coexistence of interchanging ClpP conformations with different affinities for ClpA...
  83. pmc SspB delivery of substrates for ClpXP proteolysis probed by the design of improved degradation tags
    Greg L Hersch
    Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Proc Natl Acad Sci U S A 101:12136-41. 2004
    ..This obstruct-then-stimulate mechanism may have evolved to allow additional levels of regulation and could be a common trait of adaptor-mediated protein degradation...
  84. ncbi MurAA, catalysing the first committed step in peptidoglycan biosynthesis, is a target of Clp-dependent proteolysis in Bacillus subtilis
    Holger Kock
    Ernst Moritz Arndt Universitat Greifswald, Institut fur Mikrobiologie und Molekularbiologie, Germany
    Mol Microbiol 51:1087-102. 2004
    ..Its function as a regulatory metabolic checkpoint resembles that of homoserine trans-succinylase (MetA) in E. coli which is similarly ATP-dependently degraded...
  85. ncbi Clp protease complexes from photosynthetic and non-photosynthetic plastids and mitochondria of plants, their predicted three-dimensional structures, and functional implications
    Jean Benoit Peltier
    Department of Plant Biology, Cornell University, Ithaca, New York 14853, USA
    J Biol Chem 279:4768-81. 2004
    ....
  86. pmc Ligand-controlled proteolysis of the Escherichia coli transcriptional regulator ZntR
    Mihaela Pruteanu
    Massachusetts Institute of Technology, Department of Biology, 68 523, 77 Massachusetts Ave, Cambridge, MA 02139, USA
    J Bacteriol 189:3017-25. 2007
    ..Thus, we conclude that two different ligands-zinc and DNA-function together to increase ZntR stability and that ligand-controlled proteolysis of ZntR plays an important role in fine-tuning zinc homeostasis in bacteria...
  87. ncbi Proteome and transcriptome based analysis of Bacillus subtilis cells overproducing an insoluble heterologous protein
    B Jürgen
    Institute of Microbiology, Ernst Moritz Arndt University, Greifswald, Germany
    Appl Microbiol Biotechnol 55:326-32. 2001
    ..Finally, the association of the protease ClpP and its ATPase subunits ClpC and ClpX with the PorA inclusion bodies was demonstrated by means of the immunogold labelling technique...
  88. ncbi The structure of ClpP at 2.3 A resolution suggests a model for ATP-dependent proteolysis
    J Wang
    Biology Department, Brookhaven National Laboratory, Upton, New York 11973 5000, USA
    Cell 91:447-56. 1997
    ..Access to the proteolytic chamber is controlled by two axial pores, each having a minimum diameter of approximately 10 A. From the structural features of ClpP, we suggest a model for its action in degrading proteins...
  89. ncbi Degradation by proteases Lon, Clp and HtrA, of Escherichia coli proteins aggregated in vivo by heat shock; HtrA protease action in vivo and in vitro
    E Laskowska
    Department of Biochemistry, University of Gdansk, Kladki, Poland
    Mol Microbiol 22:555-71. 1996
    ..e. the S fraction) contains endogenous substrates for the heat-shock proteases tested. Their use for in vitro reaction reveals information that is in some respects different from that obtained with exogenous substrates such as casein...
  90. ncbi New insights into the ATP-dependent Clp protease: Escherichia coli and beyond
    J Porankiewicz
    Department of Plant Physiology, University of Umea, Umeå S 901 87, Sweden
    Mol Microbiol 32:449-58. 1999
    ..The goal of this review is to summarize these recent findings and to highlight those areas that remain unresolved...
  91. pmc Subunit-specific degradation of the UmuD/D' heterodimer by the ClpXP protease: the role of trans recognition in UmuD' stability
    M Gonzalez
    Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892 2725, USA
    EMBO J 19:5251-8. 2000
    ..UmuD was also shown to be capable of channeling an excess of UmuD' to ClpXP for degradation, thereby providing a mechanism whereby cells can limit error-prone DNA replication...
  92. ncbi Protein aggregation in Escherichia coli: role of proteases
    Ran Rosen
    Department of Molecular Microbiology and Biotechnology, George S Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel
    FEMS Microbiol Lett 207:9-12. 2002
    ..The results support the assumption that protein aggregates are formed from partially unfolded proteins that were not refolded by chaperones or degraded by proteases...
  93. pmc An essential protease involved in bacterial cell-cycle control
    U Jenal
    Division of Molecular Microbiology, Biozentrum, University of Basel, CH 4056 Basel, Switzerland
    EMBO J 17:5658-69. 1998
    ..In particular, CtrA negatively controls DNA replication and our findings suggest that specific degradation of the CtrA protein by the ClpXP protease contributes to G1-to-S transition in this organism...
  94. pmc The clp proteases of Bacillus subtilis are directly involved in degradation of misfolded proteins
    E Kruger
    Institut fur Mikrobiologie und Molekularbiologie, Ernst Moritz Arndt Universitat Greifswald, D 17487 Greifswald, Germany
    J Bacteriol 182:3259-65. 2000
    ..By using immunogold labeling with antibodies raised against ClpC, ClpP, and ClpX, the Clp proteins were localized in these aggregates, showing that the Clp proteins act at this level in vivo...
  95. pmc Identification and characterization of HsIV HsIU (ClpQ ClpY) proteins involved in overall proteolysis of misfolded proteins in Escherichia coli
    D Missiakas
    Centre National de Recherche Scientifique, LIDSM CBBM, Marseille, France
    EMBO J 15:6899-909. 1996
    ..Biochemical evidence suggests that HslV/ClpQ is an efficient peptidase whose activity is enhanced by HslU/CIpY in the presence of ATP...
  96. ncbi ClpP of Bacillus subtilis is required for competence development, motility, degradative enzyme synthesis, growth at high temperature and sporulation
    T Msadek
    Unité de Biochimie Microbienne, URA 1300 du Centre National de la Recherche Scientifique, Institut Pasteur, Paris, France
    Mol Microbiol 27:899-914. 1998
    ..We suggest that ClpP is involved in controlling MecA levels in the cell through proteolysis. Increased levels of MecA in the absence of ClpP are at least partly responsible for the observed pleiotropic phenotype of the delta clpP mutant...
  97. ncbi Stress induction of the Bacillus subtilis clpP gene encoding a homologue of the proteolytic component of the Clp protease and the involvement of ClpP and ClpX in stress tolerance
    U Gerth
    Institut fur Mikrobiologie und Molekularbiologie, Ernst Moritz Arndt Universitat, Greifswald, Germany
    Mol Microbiol 28:787-802. 1998
    ..Several proteins, such as GroEL, PpiB, PykA, SucD, YhfP, YqkF, YugJ and YvyD, which were found preferentially in higher amounts in both clpP and clpX mutants, might be potential substrates for the ClpXP protease...
  98. pmc SsrA-mediated tagging in Bacillus subtilis
    T Wiegert
    Institute of Genetics, University of Bayreuth, D 95440 Bayreuth, Germany
    J Bacteriol 183:3885-9. 2001
    ..HrcA remained stable only in clpX or clpP knockouts, which suggests that this ATP-dependent protease is primarily responsible for the degradation of SsrA-tagged proteins in B. subtilis...
  99. ncbi The ClpX protein of Bacillus subtilis indirectly influences RNA polymerase holoenzyme composition and directly stimulates sigma-dependent transcription
    J Liu
    Department of Biochemistry and Molecular Biology, Oregon Graduate Institute of Science and Technology, Beaverton 97006, USA Health Sciences Cen
    Mol Microbiol 37:885-97. 2000
    ..ClpX is proposed to function indirectly in the displacement of sigmaA from core RNAP and to act directly in the stimulation of sigmaH-dependent transcription in sporulating B. subtilis cells...
  100. ncbi Distinctive types of ATP-dependent Clp proteases in cyanobacteria
    Tara M Stanne
    Department of Plant and Environmental Science, Gothenburg University, Gothenburg, Sweden
    J Biol Chem 282:14394-402. 2007
    ..Altogether, we show that presence of several distinctive Clp proteases in cyanobacteria, a feature which contrasts from that in most other organisms...
  101. pmc The RssB response regulator directly targets sigma(S) for degradation by ClpXP
    Y Zhou
    Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 4255, USA
    Genes Dev 15:627-37. 2001
    ....

Research Grants7

  1. Energy Landscapes for Acetylcholine Receptor Gating
    Stuart Licht; Fiscal Year: 2002
    ..Site- directed mutagenesis, variation of ligand occupancy, and control of transmembrane voltage will be used to perturb the gating equilibrium for the linear free energy relationship analysis. ..
  2. Bacterial Response to Singlet Oxygen
    Timothy Donohue; Fiscal Year: 2009
    ..The use of [1]O2 by eukaryotic cells to defend against pathogenic microbes and in photodynamic therapy to kill cancer cells predicts that our findings will have large antimicrobial and therapeutic potential. ..
  3. mazEF-mediated programmed cell death network in E. coli
    Hanna Engelberg Kulka; Fiscal Year: 2010
    ..Practically, the results of our study may be useful as a basis for a novel strategy for generating a new class of antibiotics that trigger bacterial PCD, and thereby to help what has become a public health problem. ..
  4. Rat, a regulator of autolysis in S. aureus
    Ambrose Cheung; Fiscal Year: 2008
    ..Our long-term goal is to promote autolysis with an anti-Rat or pro-SarV strategy without developing an untoward impact on virulence. ..
  5. Binding and regulation mechanism for S aureus
    Ambrose Cheung; Fiscal Year: 2006
    ..An understanding of these mechanisms will facilitate the development of novel agents that interfere with the function of the SarA family and the ensuing synthesis of cell wall adhesins and toxins. ..
  6. IN VIVO GENE EXPRESSION IN STAPHYLOCCUS AUREUS
    Ambrose Cheung; Fiscal Year: 2009
    ..Upon the completion of these studies, we hope to understand how sae is activated in vivo and what target genes sae impacts during infection. ..