ROBERT JOHN COLLIER

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. ncbi request reprint Anthrax toxin
    R John Collier
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Cell Dev Biol 19:45-70. 2003
  2. ncbi request reprint Understanding the mode of action of diphtheria toxin: a perspective on progress during the 20th century
    R J Collier
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Toxicon 39:1793-803. 2001
  3. pmc Membrane translocation by anthrax toxin
    R John Collier
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, United States
    Mol Aspects Med 30:413-22. 2009
  4. ncbi request reprint Mapping the anthrax protective antigen binding site on the lethal and edema factors
    D Borden Lacy
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 277:3006-10. 2002
  5. ncbi request reprint Whole-cell voltage clamp measurements of anthrax toxin pore current
    Joshua T Wolfe
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 280:39417-22. 2005
  6. pmc Disulfide bonds in the ectodomain of anthrax toxin receptor 2 are required for the receptor-bound protective-antigen pore to function
    Jianjun Sun
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 5:e10553. 2010
  7. pmc Effects of introducing a single charged residue into the phenylalanine clamp of multimeric anthrax protective antigen
    Blythe E Janowiak
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 285:8130-7. 2010
  8. ncbi request reprint Insertion of anthrax protective antigen into liposomal membranes: effects of a receptor
    Jianjun Sun
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 282:1059-65. 2007
  9. pmc Membrane insertion by anthrax protective antigen in cultured cells
    Maen Qa'Dan
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave, Boston, Massachusetts 02115, USA
    Mol Cell Biol 25:5492-8. 2005
  10. pmc A phenylalanine clamp catalyzes protein translocation through the anthrax toxin pore
    Bryan A Krantz
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Science 309:777-81. 2005

Research Grants

  1. MOLECULAR MECHANISMS OF BACTERIAL PATHOGENESIS
    ROBERT JOHN COLLIER; Fiscal Year: 2010
  2. MOLECULAR MECHANISMS OF BACTERIAL PATHOGENESIS
    Robert Collier; Fiscal Year: 2007
  3. MOLECULAR MECHANISMS OF BACTERIAL PATHOGENESIS
    Robert Collier; Fiscal Year: 2009

Collaborators

Detail Information

Publications44

  1. ncbi request reprint Anthrax toxin
    R John Collier
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Cell Dev Biol 19:45-70. 2003
    ..Knowledge of the structure and mode of action of the toxin has unveiled potential applications in medicine, including approaches to treating anthrax infections...
  2. ncbi request reprint Understanding the mode of action of diphtheria toxin: a perspective on progress during the 20th century
    R J Collier
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Toxicon 39:1793-803. 2001
    ..In this review, I present a chronology of major discoveries that led to our current understanding of the structure and activity of diphtheria toxin...
  3. pmc Membrane translocation by anthrax toxin
    R John Collier
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, United States
    Mol Aspects Med 30:413-22. 2009
    ..This transport mechanism of the pore may function in concert with molecular chaperonins to effect delivery of effector proteins in catalytically active form to the cytosolic compartment of host cells...
  4. ncbi request reprint Mapping the anthrax protective antigen binding site on the lethal and edema factors
    D Borden Lacy
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 277:3006-10. 2002
    ..The seven mutation-sensitive amino acids are clustered on the surface of LF and form a small convoluted patch with both hydrophobic and hydrophilic character. We propose that this patch constitutes the recognition site for PA...
  5. ncbi request reprint Whole-cell voltage clamp measurements of anthrax toxin pore current
    Joshua T Wolfe
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 280:39417-22. 2005
    ..These studies demonstrated basic biophysical properties of PA pores in cell membranes and served as a foundation for the study of LF and EF translocation in vivo...
  6. pmc Disulfide bonds in the ectodomain of anthrax toxin receptor 2 are required for the receptor-bound protective-antigen pore to function
    Jianjun Sun
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 5:e10553. 2010
    ..Potential roles of the receptor Ig domain in anthrax toxin action have not been investigated heretofore...
  7. pmc Effects of introducing a single charged residue into the phenylalanine clamp of multimeric anthrax protective antigen
    Blythe E Janowiak
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 285:8130-7. 2010
    ..Our findings are discussed in relation to the role of the Phe clamp in a Brownian ratchet model of translocation...
  8. ncbi request reprint Insertion of anthrax protective antigen into liposomal membranes: effects of a receptor
    Jianjun Sun
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 282:1059-65. 2007
    ....
  9. pmc Membrane insertion by anthrax protective antigen in cultured cells
    Maen Qa'Dan
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave, Boston, Massachusetts 02115, USA
    Mol Cell Biol 25:5492-8. 2005
    ..Besides supporting the beta-barrel model of membrane insertion, our results describe the time course of insertion and identify PA residues where NBD gives a strong signal upon membrane insertion in vivo...
  10. pmc A phenylalanine clamp catalyzes protein translocation through the anthrax toxin pore
    Bryan A Krantz
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Science 309:777-81. 2005
    ..We conclude that the phi clamp serves a chaperone-like function, interacting with hydrophobic sequences presented by the protein substrate as it unfolds during translocation...
  11. pmc A loop network within the anthrax toxin pore positions the phenylalanine clamp in an active conformation
    Roman A Melnyk
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:9802-7. 2006
    ..We propose that the interaction between residues 397 and 426 creates a structural framework that positions Phe-427 within the pore lumen, forming a functional Phe clamp and, hence, a translocation-competent pore...
  12. ncbi request reprint Mutant anthrax toxin B moiety (protective antigen) inhibits angiogenesis and tumor growth
    Michael S Rogers
    Vascular Biology Program and Department of Ophthalmology, Children s Hospital, and Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Cancer Res 67:9980-5. 2007
    ..These results also suggest that endothelial cell-binding proteins from additional pathogens may inhibit angiogenesis and raise the question of the role of such inhibition in pathogenesis...
  13. pmc Phenylalanine-427 of anthrax protective antigen functions in both pore formation and protein translocation
    Jianjun Sun
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:4346-51. 2008
    ..These findings demonstrate the dual functions of F427 and underline its central role in transporting the enzymatic moieties of anthrax toxin across membranes...
  14. ncbi request reprint Anthrax toxin complexes: heptameric protective antigen can bind lethal factor and edema factor simultaneously
    Ruth Anne L Pimental
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA
    Biochem Biophys Res Commun 322:258-62. 2004
    ..In view of the known maximum occupancy of 3 ligand molecules per [PA(63)](7), these findings indicate that PA, EF, and LF can form mixtures of liganded toxin complexes containing both EF and LF...
  15. pmc An approach to characterizing single-subunit mutations in multimeric prepores and pores of anthrax protective antigen
    Blythe E Janowiak
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Protein Sci 18:348-58. 2009
    ....
  16. ncbi request reprint Stoichiometry of anthrax toxin complexes
    Jeremy Mogridge
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Biochemistry 41:1079-82. 2002
    ..These results contribute to the conceptual framework for understanding the mechanism of membrane translocation by anthrax toxin...
  17. pmc Mapping the lethal factor and edema factor binding sites on oligomeric anthrax protective antigen
    Kristina Cunningham
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:7049-53. 2002
    ..These results elucidate the process by which the components of anthrax toxin, and perhaps other binary bacterial toxins, assemble into toxic complexes...
  18. ncbi request reprint The structural basis for substrate and inhibitor selectivity of the anthrax lethal factor
    Benjamin E Turk
    Division of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
    Nat Struct Mol Biol 11:60-6. 2004
    ..The crystal structures of LF bound to an optimized peptide substrate and to peptide-based inhibitors provide a rationale for the observed selectivity and may be exploited in the design of future generations of LF inhibitors...
  19. pmc A semisynthesis platform for investigating structure-function relationships in the N-terminal domain of the anthrax Lethal Factor
    Brad L Pentelute
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    ACS Chem Biol 5:359-64. 2010
    ..The semisynthesis platform thus makes new analytical approaches available to investigate the interaction of the pore with its substrates...
  20. ncbi request reprint Protein translocation through the anthrax toxin transmembrane pore is driven by a proton gradient
    Bryan A Krantz
    Department of Microbiology and Molecular Genetics, Harvard Medical School 200 Longwood Ave, Boston, MA 02115, USA
    J Mol Biol 355:968-79. 2006
    ..In a sense, the channel functions as a proton/protein symporter...
  21. pmc The lethal and edema factors of anthrax toxin bind only to oligomeric forms of the protective antigen
    Jeremy Mogridge
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 99:7045-8. 2002
    ..Thus EF and LF bind stably only to PA(63) dimers or higher order oligomers. These findings are relevant to the kinetics and pathways of assembly of anthrax toxin complexes...
  22. ncbi request reprint Exchange characteristics of calcium ions bound to anthrax protective antigen
    Samantha Gao-Sheridan
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Biochem Biophys Res Commun 300:61-4. 2003
    ..These results are consistent with the hypothesis that bound Ca(2+) within PA plays primarily a structural role, maintaining domain 1(') in a conformation that allows PA(63) to oligomerize and bind the enzymatic moieties of the toxin...
  23. pmc Cross-linked forms of the isolated N-terminal domain of the lethal factor are potent inhibitors of anthrax toxin
    Stephen J Juris
    Harvard Medical School, Department of Microbiology and Molecular Genetics, 200 Longwood Avenue, Boston, MA 02115, USA
    Infect Immun 75:5052-8. 2007
    ..These findings show that the PA pore cannot translocate multimeric, cross-linked polypeptides and demonstrate a new approach to generating potent inhibitors of anthrax toxin...
  24. pmc Evidence that translocation of anthrax toxin's lethal factor is initiated by entry of its N terminus into the protective antigen channel
    Sen Zhang
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:16756-61. 2004
    ....
  25. pmc Structure of heptameric protective antigen bound to an anthrax toxin receptor: a role for receptor in pH-dependent pore formation
    D Borden Lacy
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:13147-51. 2004
    ..We present an example of a receptor negatively regulating pH-dependent membrane insertion...
  26. pmc Anthrax lethal toxin induces cell death-independent permeability in zebrafish vasculature
    Robert E Bolcome
    Vascular Biology Program, Children s Hospital Boston and Department of Surgery, Harvard Medical School, Boston, MA 02115
    Proc Natl Acad Sci U S A 105:2439-44. 2008
    ..Our study demonstrates the importance of vascular permeability in anthrax lethal toxin action and the need for further investigation of the cardiovascular component of human anthrax disease...
  27. pmc Solubilization and characterization of the anthrax toxin pore in detergent micelles
    Gregory Vernier
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave, Boston, Massachusetts 02115, USA
    Protein Sci 18:1882-95. 2009
    ..Stabilizing the PA pore in solution with FOS14 may facilitate further structural analysis and a more detailed understanding of the folding pathway by which the pore is formed...
  28. pmc Assembly and disassembly kinetics of anthrax toxin complexes
    Kenneth A Christensen
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Biochemistry 45:2380-6. 2006
    ..A self-assembly scheme of anthrax toxin complexes is proposed...
  29. pmc Functions of phenylalanine residues within the beta-barrel stem of the anthrax toxin pore
    Jie Wang
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 4:e6280. 2009
    ..Formation of this transmembrane pore by PA involves interaction of the seven 2beta2-2beta3 loops of the heptameric precursor to generate a 14-strand transmembrane beta barrel...
  30. ncbi request reprint Structural determinants for the binding of anthrax lethal factor to oligomeric protective antigen
    Roman A Melnyk
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 281:1630-5. 2006
    ..Our results elucidate the structural basis for anthrax lethal toxin assembly and may be useful in developing drugs to block toxin action...
  31. pmc A dually active anthrax vaccine that confers protection against both bacilli and toxins
    Gi Eun Rhie
    Department of Microbiology and Molecular Genetics, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:10925-30. 2003
    ..DAAV introduces a vaccine design that may be widely applicable against infectious diseases and provides additional tools in medicine and biodefense...
  32. pmc Mapping dominant-negative mutations of anthrax protective antigen by scanning mutagenesis
    Michael Mourez
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:13803-8. 2003
    ..They also add to the repertoire of mutations available for structure-function studies and for designing new antitoxic agents for treatment of anthrax...
  33. ncbi request reprint Binding stoichiometry and kinetics of the interaction of a human anthrax toxin receptor, CMG2, with protective antigen
    Darran J Wigelsworth
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 279:23349-56. 2004
    ..The high affinity of the VWA domain for PA supports its potency in neutralizing anthrax toxin, demonstrating its potential utility as a novel therapeutic for anthrax...
  34. ncbi request reprint Use of phage display and polyvalency to design inhibitors of protein-protein interactions
    Michael Mourez
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA, USA
    Methods Mol Biol 261:213-28. 2004
    ..Because little structural knowledge of the interacting proteins was required to synthesize this inhibitor, we believe that this approach may prove useful in the design of inhibitors of protein-protein interactions in other systems...
  35. pmc Protein translocation through anthrax toxin channels formed in planar lipid bilayers
    Sen Zhang
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, USA
    Biophys J 87:3842-9. 2004
    ....
  36. ncbi request reprint Effects of dynamin inactivation on pathways of anthrax toxin uptake
    Werner Boll
    Department of Cell Biology, The CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA
    Eur J Cell Biol 83:281-8. 2004
    ..In contrast, a long-term block of dynamin activity results in a further interference with LFn-DTA toxicity that is consistent with an altered endosomal environment, probably an increase in endosomal pH...
  37. ncbi request reprint Acid-induced unfolding of the amino-terminal domains of the lethal and edema factors of anthrax toxin
    Bryan A Krantz
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115, USA
    J Mol Biol 344:739-56. 2004
    ..Finally, analysis of the structure of the transmembrane beta-barrel of PA shows that it can accommodate alpha-helix, and we suggest that the steric constraints and composition of the lumen may promote alpha-helix formation...
  38. ncbi request reprint 2001: a year of major advances in anthrax toxin research
    Michael Mourez
    Dept of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA
    Trends Microbiol 10:287-93. 2002
    ..These findings have improved our understanding of the intoxication mechanism and are stimulating the design of strategies to fight disease in the future...
  39. pmc Characterization of dominant-negative forms of anthrax protective antigen
    Ming Yan
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Mol Med 9:46-51. 2003
    ..The properties of the double and the triple mutants make these forms worthy of testing in vivo as a new type of antitoxic agent for treatment of anthrax...
  40. ncbi request reprint Conformational changes in BID, a pro-apoptotic BCL-2 family member, upon membrane binding. A site-directed spin labeling study
    Kyoung Joon Oh
    Howard Hughes Medical Institute, the Department of Pathology and Medicine, Harvard Medical School, Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Biol Chem 280:753-67. 2005
    ..Our study presents a more detailed model for the reorganization of the structure of tBID on membranes...
  41. ncbi request reprint Interaction of the 20 kDa and 63 kDa fragments of anthrax protective antigen: kinetics and thermodynamics
    Kenneth A Christensen
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Biochemistry 44:1047-53. 2005
    ..A slow isomerization step in PA(63) may then potentiate it for oligomerization and subsequent steps in toxin action...
  42. pmc Combining anthrax vaccine and therapy: a dominant-negative inhibitor of anthrax toxin is also a potent and safe immunogen for vaccines
    Benedikt A Aulinger
    Channing Laboratory, Department of Medicine, Brigham and Women s Hospital, 181 Longwood Avenue, Boston, MA 02115, USA
    Infect Immun 73:3408-14. 2005
    ..Because DNI has previously been demonstrated to inhibit anthrax toxin, postexposure use of DNI-based vaccines, including conjugate vaccines, may provide improved immunogenicity and therapeutic activity simultaneously...
  43. pmc A model of anthrax toxin lethal factor bound to protective antigen
    D Borden Lacy
    Department of Microbiology and Molecular Genetics and Graduate Group of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:16409-14. 2005
    ....
  44. pmc Crystal structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptor
    D Borden Lacy
    Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:6367-72. 2004
    ..The structural data also allow molecular interpretation of known CMG2 VWA domain mutations linked to the genetic disorders, juvenile hyaline fibromatosis, and infantile systemic hyalinosis...

Research Grants4

  1. MOLECULAR MECHANISMS OF BACTERIAL PATHOGENESIS
    ROBERT JOHN COLLIER; Fiscal Year: 2010
    ..As with our past research, these studies are expected to yield findings relevant to uses of toxins in medical applications. ..
  2. MOLECULAR MECHANISMS OF BACTERIAL PATHOGENESIS
    Robert Collier; Fiscal Year: 2007
    ..abstract_text> ..
  3. MOLECULAR MECHANISMS OF BACTERIAL PATHOGENESIS
    Robert Collier; Fiscal Year: 2009
    ..As with our past research, these studies are expected to yield findings relevant to uses of toxins in medical applications. ..