Sinisa Urban

Summary

Affiliation: Johns Hopkins University
Country: USA

Publications

  1. pmc Membrane immersion allows rhomboid proteases to achieve specificity by reading transmembrane segment dynamics
    Syed M Moin
    Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University, Baltimore, United States
    elife 1:e00173. 2012
  2. doi request reprint Mechanisms and cellular functions of intramembrane proteases
    Sinisa Urban
    Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA Electronic address
    Biochim Biophys Acta 1828:2797-800. 2013
  3. pmc The rhomboid protease family: a decade of progress on function and mechanism
    Sinisa Urban
    Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Genome Biol 12:231. 2011
  4. ncbi request reprint Rhomboid proteins: conserved membrane proteases with divergent biological functions
    Sinisa Urban
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Genes Dev 20:3054-68. 2006
  5. pmc Core principles of intramembrane proteolysis: comparison of rhomboid and site-2 family proteases
    Sinisa Urban
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Curr Opin Struct Biol 18:432-41. 2008
  6. pmc In vivo analysis reveals substrate-gating mutants of a rhomboid intramembrane protease display increased activity in living cells
    Sinisa Urban
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 507 PCTB, 725 North Wolfe Street, Baltimore, MD 21205, USA
    Biol Chem 389:1107-15. 2008
  7. pmc Making the cut: central roles of intramembrane proteolysis in pathogenic microorganisms
    Sinisa Urban
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nat Rev Microbiol 7:411-23. 2009
  8. pmc Taking the plunge: integrating structural, enzymatic and computational insights into a unified model for membrane-immersed rhomboid proteolysis
    Sinisa Urban
    Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Biochem J 425:501-12. 2010
  9. pmc Enzymatic analysis of a rhomboid intramembrane protease implicates transmembrane helix 5 as the lateral substrate gate
    Rosanna P Baker
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 507 Preclinical Teaching Building, 725 North Wolfe Street, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 104:8257-62. 2007
  10. ncbi request reprint Proteolysis inside the membrane is a rate-governed reaction not driven by substrate affinity
    Seth W Dickey
    Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Room 507 PCTB, 725 North Wolfe Street, Baltimore, MD 21205, USA
    Cell 155:1270-81. 2013

Collaborators

  • Michael Wolfe
  • M Freeman
  • Yigong Shi
  • Rosanna P Baker
  • Seth W Dickey
  • Syed M Moin
  • Leigh A Baxt
  • Liang Feng
  • Zhuoru Wu
  • Fabien Brossier
  • Masahiro M Kanaoka
  • Olli Lohi
  • Sangwoo Cho
  • Upinder Singh
  • Keith Young
  • Philip D Jeffrey
  • Lichuan Gu
  • Hanchi Yan
  • Nieng Yan
  • Ruvini Wijetilaka
  • Adam Oberstein
  • Travis J Jewett
  • Kiyotaka Okada
  • L David Sibley

Detail Information

Publications22

  1. pmc Membrane immersion allows rhomboid proteases to achieve specificity by reading transmembrane segment dynamics
    Syed M Moin
    Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University, Baltimore, United States
    elife 1:e00173. 2012
    ..Membrane immersion thus bestows rhomboid proteases with the ability to identify substrates primarily based on reading their intrinsic transmembrane dynamics.DOI:http://dx.doi.org/10.7554/eLife.00173.001...
  2. doi request reprint Mechanisms and cellular functions of intramembrane proteases
    Sinisa Urban
    Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, 21205, USA Electronic address
    Biochim Biophys Acta 1828:2797-800. 2013
    ..Recent studies also expose challenges for the future, including non-linear relationships between substrate identification and physiological functions, and the need for potent and specific, not broad-class, inhibitors. ..
  3. pmc The rhomboid protease family: a decade of progress on function and mechanism
    Sinisa Urban
    Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Genome Biol 12:231. 2011
    ..Rhomboid proteases are unlike most proteolytic enzymes, because they are membrane-immersed; understanding how the membrane immersion affects their function remains a key challenge...
  4. ncbi request reprint Rhomboid proteins: conserved membrane proteases with divergent biological functions
    Sinisa Urban
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Genes Dev 20:3054-68. 2006
    ..Further study of these novel enzymes promises to reveal the evolutionary path of rhomboid protein function, which could provide insights into the forces that drive the molecular evolution of regulatory mechanisms...
  5. pmc Core principles of intramembrane proteolysis: comparison of rhomboid and site-2 family proteases
    Sinisa Urban
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Curr Opin Struct Biol 18:432-41. 2008
    ..We focus on detailing the similarities between these unrelated enzymes to define core biochemical principles that govern this conserved regulatory mechanism...
  6. pmc In vivo analysis reveals substrate-gating mutants of a rhomboid intramembrane protease display increased activity in living cells
    Sinisa Urban
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 507 PCTB, 725 North Wolfe Street, Baltimore, MD 21205, USA
    Biol Chem 389:1107-15. 2008
    ..These observations provide evidence for the existence of both closed and open forms of GlpG in cells, and show that inter-conversion between them via substrate gating is rate limiting physiologically...
  7. pmc Making the cut: central roles of intramembrane proteolysis in pathogenic microorganisms
    Sinisa Urban
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Nat Rev Microbiol 7:411-23. 2009
    ..This Review focuses on summarizing the advances, evaluating the limitations and highlighting the promise of this newly emerging field...
  8. pmc Taking the plunge: integrating structural, enzymatic and computational insights into a unified model for membrane-immersed rhomboid proteolysis
    Sinisa Urban
    Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Biochem J 425:501-12. 2010
    ..Although far from complete, studies with GlpG currently offer the best prospect for achieving a thorough and sophisticated understanding of a simplified intramembrane protease...
  9. pmc Enzymatic analysis of a rhomboid intramembrane protease implicates transmembrane helix 5 as the lateral substrate gate
    Rosanna P Baker
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 507 Preclinical Teaching Building, 725 North Wolfe Street, Baltimore, MD 21205, USA
    Proc Natl Acad Sci U S A 104:8257-62. 2007
    ..Moreover, our mutagenesis also underscores the importance of other residue interactions within the enzyme that warrant further scrutiny...
  10. ncbi request reprint Proteolysis inside the membrane is a rate-governed reaction not driven by substrate affinity
    Seth W Dickey
    Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Room 507 PCTB, 725 North Wolfe Street, Baltimore, MD 21205, USA
    Cell 155:1270-81. 2013
    ..These properties are unlike those of other studied proteases or membrane proteins but are strikingly reminiscent of one subset of DNA-repair enzymes, raising important mechanistic and drug-design implications...
  11. pmc Two Plasmodium rhomboid proteases preferentially cleave different adhesins implicated in all invasive stages of malaria
    Rosanna P Baker
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
    PLoS Pathog 2:e113. 2006
    ..This is the first enzymatic analysis of Plasmodium rhomboid proteases and suggests an involvement of PfROMs in all invasive stages of the malaria lifecycle, in both the vertebrate host and the mosquito vector...
  12. ncbi request reprint Architectural and thermodynamic principles underlying intramembrane protease function
    Rosanna P Baker
    Howard Hughes Medical Institute, Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Nat Chem Biol 8:759-68. 2012
    ..Our analyses provide a comprehensive 'heat map' of the physiochemical anatomy underlying membrane-immersed enzyme function at, what is to our knowledge, unprecedented resolution...
  13. ncbi request reprint Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry
    Zhuoru Wu
    Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, New Jersey 08544, USA
    Nat Struct Mol Biol 13:1084-91. 2006
    ..Structural analysis suggests that substrate entry to the active site is probably gated by the movement of helix alpha5...
  14. ncbi request reprint Conservation of intramembrane proteolytic activity and substrate specificity in prokaryotic and eukaryotic rhomboids
    Sinisa Urban
    MRC Laboratory of Molecular Biology, Cambridge, CB2 2QH, United Kingdom
    Curr Biol 12:1507-12. 2002
    ..Moreover, a function for Rhomboids in activating intercellular signaling appears to have evolved early...
  15. ncbi request reprint Substrate specificity of rhomboid intramembrane proteases is governed by helix-breaking residues in the substrate transmembrane domain
    Sinisa Urban
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom
    Mol Cell 11:1425-34. 2003
    ..These results provide an explanation of how rhomboid proteases achieve specificity, and allow some rhomboid substrates to be predicted from sequence information...
  16. ncbi request reprint EGF receptor signalling protects smooth-cuticle cells from apoptosis during Drosophila ventral epidermis development
    Sinisa Urban
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Development 131:1835-45. 2004
    ..This strategy might guard against developmental errors, and may be conserved in mammalian epidermal patterning...
  17. pmc Reconstitution of intramembrane proteolysis in vitro reveals that pure rhomboid is sufficient for catalysis and specificity
    Sinisa Urban
    Center for Neurologic Diseases, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:1883-8. 2005
    ..This analysis promises to help reveal the biochemical mechanisms and biological roles of this most widely conserved membrane protein family...
  18. pmc A spatially localized rhomboid protease cleaves cell surface adhesins essential for invasion by Toxoplasma
    Fabien Brossier
    Department of Molecular Microbiology, Center for Infectious Diseases, Washington University School of Medicine, St Louis, MO 63110 1093, USA
    Proc Natl Acad Sci U S A 102:4146-51. 2005
    ..T. gondii rhomboids have clear homologues in other apicomplexans including malaria; thus, our findings provide a model for studying invasion by this deadly pathogen and offer a target for therapeutic intervention...
  19. ncbi request reprint An Arabidopsis Rhomboid homolog is an intramembrane protease in plants
    Masahiro M Kanaoka
    Department of Botany, Graduate School of Science, Kyoto University, Kitashirakawa Oiwake cho, Sakyo ku, Japan
    FEBS Lett 579:5723-8. 2005
    ..These studies provide the first evidence that the determinants of RIP are present in plants...
  20. pmc A family of Rhomboid intramembrane proteases activates all Drosophila membrane-tethered EGF ligands
    Sinisa Urban
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    EMBO J 21:4277-86. 2002
    ..This is distinct from the metalloprotease-induced activation of mammalian EGF-like ligands...
  21. ncbi request reprint Diverse substrate recognition mechanisms for rhomboids; thrombomodulin is cleaved by Mammalian rhomboids
    Olli Lohi
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom
    Curr Biol 14:236-41. 2004
    ..Moreover, the discovery of a second mode of substrate recognition by rhomboids implies mechanistic diversity in this family of intramembrane proteases...
  22. pmc An Entamoeba histolytica rhomboid protease with atypical specificity cleaves a surface lectin involved in phagocytosis and immune evasion
    Leigh A Baxt
    Department of Internal Medicine and Microbiology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Genes Dev 22:1636-46. 2008
    ..Collectively these results implicate rhomboid proteases for the first time in immune evasion and suggest that a common function of rhomboid enzymes in widely divergent protozoan pathogens is to break down adhesion proteins...

Research Grants6