| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 276, Issue 46, 42667-42676, November 16, 2001
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Human and simian immunodeficiency viruses infect
host lymphoid cells by binding CD4 molecules via their gp160 envelope
glycoproteins. Biochemical studies on recombinant SIVmac32H (pJ5)
envelope ectodomain gp140 precursor protein show that the envelope is a
trimer. Using size exclusion chromatography, quantitative amino acid
analysis, analytical ultracentrifugation, and CD4-based competition
assay, we demonstrate that the stoichiometry of CD4 receptor-oligomeric envelope interaction is 1:1. By contrast, Fab fragments of both neutralizing and non-neutralizing monoclonal antibodies bind at a 3:1 ratio. Thus, despite displaying equivalent CD4 binding sites on
each of the three gp140 protomers within an uncleaved trimer, only one
site binds the soluble 4-domain human CD4 extracellular segment. The
anti-cooperativity and the faster koff of gp140
trimer:CD4 versus gp120 monomer:CD4 interaction suggest
that CD4-induced conformational change is impeded in the intact
envelope. The implications of these findings for immunity against human
immunodeficiency virus and simian immunodeficiency virus are discussed.
The Stoichiometry of Trimeric SIV Glycoprotein Interaction with
CD4 Differs from That of Anti-envelope Antibody Fab Fragments*
,,,
,
Laboratory of Immunobiology, Dana-Farber
Cancer Institute and Department of Medicine, Harvard Medical School,
Boston, Massachusetts 02115, the § Laboratory of Molecular
Medicine, The Children's Hospital, Howard Hughes Medical Institute,
Boston, Massachusetts 02115, the ¶ Department of Surgery, Duke
University Medical School, Durham, North Carolina 27710, the
Department of Medicine, University of Pennsylvania,
Philadelphia, Pennsylvania 19104, and the ** Division of
Infection and Immunity, Institute of Biomedical and Life Sciences,
University of Glasgow, Glasgow G12 8QQ, United Kingdom
*
This work was supported by Novel HIV Therapy-ICHP
Grant AI43649 (to E. L. R. and S. C. H.), an Innovation Grant (to
S. C. H.), the Howard Hughes Medical Institute, and National
Institutes of Health Grant AI85343 (to D. M.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dana-Farber Cancer
Inst., 44 Binney St., Boston, MA 02115; Tel.: 617-632-3412; Fax:
617-632-3351; E-mail: ellis_reinherz@dfci.harvard.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Frey, H. Peng, S. Rits-Volloch, M. Morelli, Y. Cheng, and B. Chen A fusion-intermediate state of HIV-1 gp41 targeted by broadly neutralizing antibodies PNAS, March 11, 2008; 105(10): 3739 - 3744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yang, S. Kurteva, X. Ren, S. Lee, and J. Sodroski Subunit Stoichiometry of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trimers during Virus Entry into Host Cells J. Virol., May 1, 2006; 80(9): 4388 - 4395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Pancera, J. Lebowitz, A. Schon, P. Zhu, E. Freire, P. D. Kwong, K. H. Roux, J. Sodroski, and R. Wyatt Soluble Mimetics of Human Immunodeficiency Virus Type 1 Viral Spikes Produced by Replacement of the Native Trimerization Domain with a Heterologous Trimerization Motif: Characterization and Ligand Binding Analysis J. Virol., August 1, 2005; 79(15): 9954 - 9969. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-S. Qiao, M. Kim, B. Reinhold, D. Montefiori, J.-h. Wang, and E. L. Reinherz Design, Expression, and Immunogenicity of a Soluble HIV Trimeric Envelope Fragment Adopting a Prefusion gp41 Configuration J. Biol. Chem., June 17, 2005; 280(24): 23138 - 23146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Delos, J. A. Godby, and J. M. White Receptor-Induced Conformational Changes in the SU Subunit of the Avian Sarcoma/Leukosis Virus A Envelope Protein: Implications for Fusion Activation J. Virol., March 15, 2005; 79(6): 3488 - 3499. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Yang, S. Kurteva, S. Lee, and J. Sodroski Stoichiometry of Antibody Neutralization of Human Immunodeficiency Virus Type 1 J. Virol., March 15, 2005; 79(6): 3500 - 3508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Gao, E. A. Weaver, Z. Lu, Y. Li, H.-X. Liao, B. Ma, S. M. Alam, R. M. Scearce, L. L. Sutherland, J.-S. Yu, et al. Antigenicity and Immunogenicity of a Synthetic Human Immunodeficiency Virus Type 1 Group M Consensus Envelope Glycoprotein J. Virol., January 15, 2005; 79(2): 1154 - 1163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kim, H. Yang, S.-K. Kim, P. A. Reche, R. S. Tirabassi, R. E. Hussey, Y. Chishti, J. G. Rheinwald, T. J. Morehead, T. Zech, et al. Biochemical and Functional Analysis of Smallpox Growth Factor (SPGF) and Anti-SPGF Monoclonal Antibodies J. Biol. Chem., June 11, 2004; 279(24): 25838 - 25848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Chen, Y. Cheng, L. Calder, S. C. Harrison, E. L. Reinherz, J. J. Skehel, and D. C. Wiley A Chimeric Protein of Simian Immunodeficiency Virus Envelope Glycoprotein gp140 and Escherichia coli Aspartate Transcarbamoylase J. Virol., May 1, 2004; 78(9): 4508 - 4516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. N. Lewicki and T. M. Gallagher Quaternary Structure of Coronavirus Spikes in Complex with Carcinoembryonic Antigen-related Cell Adhesion Molecule Cellular Receptors J. Biol. Chem., May 24, 2002; 277(22): 19727 - 19734. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
