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PMID: 1896455 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Stimulation of glycoprotein gp120 dissociation from the envelope glycoprotein complex of human immunodeficiency virus type 1 by soluble CD4 and CD4 peptide derivatives: implications for the role of the complementarity-determining region 3-like region in membrane fusion.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 88 ·No. 18 ·1991-09-15 ·Pages 8082-6

Berger EA, Lifson JD, Eiden LE

Abstract

We have used a recombinant vaccinia virus vector encoding the envelope glycoprotein of human immunodeficiency virus type 1 to study receptor-induced structural changes related to membrane fusion. A truncated soluble form of human CD4 (sCD4) was found to stimulate dissociation of the external subunit (gp120) from the envelope glycoprotein complex of human immunodeficiency virus type 1 expressed at the cell surface. sCD4 stimulation of gp120 release was time- and concentration-dependent and was associated with specific binding of sCD4 to gp120. Synthetic peptide derivatives corresponding to residues 81-92 of human CD4 (overlapping the complementarity-determining region 3-like region) inhibited cell-cell fusion mediated by the interaction between recombinant vaccinia-encoded CD4 and human immunodeficiency virus envelope glycoprotein. These peptide derivatives also stimulated gp120 release from the envelope glycoprotein complex. An analogous peptide derivative from chimpanzee CD4 (containing a single Glu----Gly substitution at the position corresponding to CD4 residue 87) was considerably less active at inhibition of cell-cell fusion and stimulation of gp120 release, consistent with the known inhibitory effect of this substitution on the ability of membrane-associated CD4 to mediate cell fusion. These results suggest that the sCD4-induced release of gp120 reflects postbinding structural changes in the envelope glycoprotein complex involved in membrane fusion, with the complementarity-determining region 3-like region playing a critical role.

MeSH Terms
CD4 Antigens/chemistry,metabolism HIV Envelope Protein gp120/metabolism HeLa Cells Humans In Vitro Techniques Membrane Fusion Peptides/metabolism Protein Binding Recombinant Proteins Structure-Activity Relationship Viral Fusion Proteins/metabolism
Chemicals
CD4 Antigens HIV Envelope Protein gp120 Peptides Recombinant Proteins Viral Fusion Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Berger E A
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Lifson J D
Eiden L E
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.88.18.8082
Published
1991-09-15
Pages
8082-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC52450
Subset
IM
Grants
NIAID NIH HHS · AI25922 · United States
External Links
PubMed source DOI: 10.1073/pnas.88.18.8082 PMC Full Text View journal details
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