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Location and Chemical Synthesis of a Binding Site for HIV-1 on the CD4 Protein

Jameson, Bradford A. and Rao, Patricia E. and Kong, Lilly I. and Hahn, Beatrice H. and Shaw, George M. and Hood, Leroy E. and Kent, Stephen B. H. (1988) Location and Chemical Synthesis of a Binding Site for HIV-1 on the CD4 Protein. Science, 240 (4857). pp. 1335-1339. ISSN 0036-8075. http://resolver.caltech.edu/CaltechAUTHORS:20150206-093138132

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Abstract

The human immunodeficiency virus type 1 (HIV-1) uses the CD4 protein as a receptor for infection of susceptible cells. A candidate structure for the HIV-1 binding site on the CD4 protein was identified by epitope mapping with a family of eight functionally distinct CD4-specific monoclonal antibodies in conjunction with a panel of large CD4-derived synthetic peptides. All of the seven epitopes that were located reside within two immunoglobulin-like disulfide loops situated between residues 1 and 168 of the CD4 protein. The CD4-specific monoclonal antibody OKT4A, a potent inhibitor of HIV-1 binding, recognized a site between residues 32 and 47 on the CD4 protein. By analogy to other members of the immunoglobulin superfamily of proteins, this particular region has been predicted to exist as a protruding loop. A synthetic analog of this loop (residues 25 to 58) showed a concentration-dependent inhibition of HIV-1-induced cell fusion. It is proposed that a loop extending from residues 37 to 53 of the CD4 protein is a binding site for the AIDS virus.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1126/science.2453925DOIArticle
http://www.sciencemag.org/content/240/4857/1335PublisherArticle
http://www.jstor.org/stable/1701064 JSTORArticle
ORCID:
AuthorORCID
Hood, Leroy E.0000-0001-7158-3678
Additional Information:© 1988 American Association for the Advancement of Science. 18 February 1988; accepted 18 April 1988. Principal support for this work was provided by a Marshall Field's Award from the American Foundation for AIDS Research, grant No. 00465R (S.B.H.K.). The cell fusion assays were supported by AI25784 (G.S. and B.H.). We thank P. Rieber for MT151, D. Wernicke-Jameson for discussions, P. Dervan for the use of computer facilities, S. Perry, S. E. McAnaney, and L. Martin Selk for tec assistance, C. Elkins for manuscript typing, and D. Noskowitz for figure preparation.
Funders:
Funding AgencyGrant Number
American Foundation for AIDS Research00465R
NIHAI25784
Record Number:CaltechAUTHORS:20150206-093138132
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20150206-093138132
Official Citation:Jameson, B., Rao, P., Kong, L., Hahn, B., Shaw, G., Hood, L., & Kent, S. (1988). Location and chemical synthesis of a binding site for HIV-1 on the CD4 protein. Science, 240(4857), 1335-1339. doi: 10.1126/science.2453925
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:54471
Collection:CaltechAUTHORS
Deposited By: Jason Perez
Deposited On:06 Feb 2015 19:35
Last Modified:17 Nov 2016 20:27

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