Research Topics
| ROBERT JOHN COLLIERSummaryAffiliation: Harvard University Country: USA Publications
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Publications
Anthrax toxinR 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...- Understanding the mode of action of diphtheria toxin: a perspective on progress during the 20th centuryR 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... 
Membrane translocation by anthrax toxinR 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...- Mapping the anthrax protective antigen binding site on the lethal and edema factorsD 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... - Whole-cell voltage clamp measurements of anthrax toxin pore currentJoshua 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... - Disulfide bonds in the ectodomain of anthrax toxin receptor 2 are required for the receptor-bound protective-antigen pore to functionJianjun 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... - Effects of introducing a single charged residue into the phenylalanine clamp of multimeric anthrax protective antigenBlythe 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... - Insertion of anthrax protective antigen into liposomal membranes: effects of a receptorJianjun Sun
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 282:1059-65. 2007.... - Membrane insertion by anthrax protective antigen in cultured cellsKenneth A Christensen
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... - A phenylalanine clamp catalyzes protein translocation through the anthrax toxin poreBryan 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... - A loop network within the anthrax toxin pore positions the phenylalanine clamp in an active conformationRoman 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... - Mutant anthrax toxin B moiety (protective antigen) inhibits angiogenesis and tumor growthMichael 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... - Phenylalanine-427 of anthrax protective antigen functions in both pore formation and protein translocationJianjun 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... - Anthrax toxin complexes: heptameric protective antigen can bind lethal factor and edema factor simultaneouslyRuth-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... - An approach to characterizing single-subunit mutations in multimeric prepores and pores of anthrax protective antigenBlythe E Janowiak
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
Protein Sci 18:348-58. 2009.... - Stoichiometry of anthrax toxin complexesJeremy 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... - Mapping the lethal factor and edema factor binding sites on oligomeric anthrax protective antigenKristina 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... - The structural basis for substrate and inhibitor selectivity of the anthrax lethal factorBenjamin 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... - A semisynthesis platform for investigating structure-function relationships in the N-terminal domain of the anthrax Lethal FactorBrad 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... - Protein translocation through the anthrax toxin transmembrane pore is driven by a proton gradientBryan 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... - The lethal and edema factors of anthrax toxin bind only to oligomeric forms of the protective antigenJeremy 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... - Exchange characteristics of calcium ions bound to anthrax protective antigenSamantha 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... - Cross-linked forms of the isolated N-terminal domain of the lethal factor are potent inhibitors of anthrax toxinStephen 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... - Evidence that translocation of anthrax toxin's lethal factor is initiated by entry of its N terminus into the protective antigen channelSen 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.... - Structure of heptameric protective antigen bound to an anthrax toxin receptor: a role for receptor in pH-dependent pore formationD 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... - Anthrax lethal toxin induces cell death-independent permeability in zebrafish vasculatureRobert 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... - Solubilization and characterization of the anthrax toxin pore in detergent micellesGregory 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... - Assembly and disassembly kinetics of anthrax toxin complexesKenneth 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... - Functions of phenylalanine residues within the beta-barrel stem of the anthrax toxin poreJie 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... - Structural determinants for the binding of anthrax lethal factor to oligomeric protective antigenRoman 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... - A dually active anthrax vaccine that confers protection against both bacilli and toxinsGi-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... - Mapping dominant-negative mutations of anthrax protective antigen by scanning mutagenesisMichael 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... - Binding stoichiometry and kinetics of the interaction of a human anthrax toxin receptor, CMG2, with protective antigenDarran 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... - Use of phage display and polyvalency to design inhibitors of protein-protein interactionsMichael 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... - Protein translocation through anthrax toxin channels formed in planar lipid bilayersSen Zhang
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, USA
Biophys J 87:3842-9. 2004.... - Effects of dynamin inactivation on pathways of anthrax toxin uptakeWerner 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... - Acid-induced unfolding of the amino-terminal domains of the lethal and edema factors of anthrax toxinBryan 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... - 2001: a year of major advances in anthrax toxin researchMichael 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... - Characterization of dominant-negative forms of anthrax protective antigenMing 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... - Conformational changes in BID, a pro-apoptotic BCL-2 family member, upon membrane binding. A site-directed spin labeling studyKyoung 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... - Interaction of the 20 kDa and 63 kDa fragments of anthrax protective antigen: kinetics and thermodynamicsKenneth 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... - Combining anthrax vaccine and therapy: a dominant-negative inhibitor of anthrax toxin is also a potent and safe immunogen for vaccinesBenedikt 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... - A model of anthrax toxin lethal factor bound to protective antigenD 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.... - Crystal structure of the von Willebrand factor A domain of human capillary morphogenesis protein 2: an anthrax toxin receptorD 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 Grants
- MOLECULAR MECHANISMS OF BACTERIAL PATHOGENESISROBERT 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. ..
- MOLECULAR MECHANISMS OF BACTERIAL PATHOGENESISRobert Collier; Fiscal Year: 2007..abstract_text> ..
- MOLECULAR MECHANISMS OF BACTERIAL PATHOGENESISRobert Collier; Fiscal Year: 2009..As with our past research, these studies are expected to yield findings relevant to uses of toxins in medical applications. ..