Scientific Publications
- PMID: 19535453
- Title: Transitions to and from the CD4 bound conformation are modulated by a single residue change in the human immunodeficiency virus type 1 gp120 inner domain
- Abstract: Binding to the primary receptor CD4 induces conformational changes in the human immunodeficiency virus type 1 (HIV-1) gp120 envelope glycoprotein that allow binding to the coreceptor (CCR5 or CXCR4) and ultimately trigger viral membrane-cell membrane fusion mediated by the gp41 transmembrane envelope glycoprotein. Here we report the derivation of an HIV-1 gp120 variant, H66N, that confers envelope glycoprotein resistance to temperature extremes. The H66N change decreases the spontaneous sampling of the CD4-bound conformation by the HIV-1 envelope glycoproteins, thus diminishing CD4-independent infection. The H66N change also stabilizes the HIV-1 envelope glycoprotein complex once the CD4-bound state is achieved, decreasing the probability of CD4-induced inactivation and revealing the enhancing effects of soluble CD4 binding on HIV-1 infection. In the CD4-bound conformation, the highly conserved histidine 66 is located between the receptor-binding and gp41-interactive surfaces of gp120. Thus, a single amino acid change in this strategically positioned gp120 inner domain residue influences the propensity of the HIV-1 envelope glycoproteins to negotiate conformational transitions to and from the CD4-bound state.
- Date: 1970-08-21
- Year: 2009
- Journal: J. Virol.
- PMID Author: Kassa A, Madani N, Schön A, Haim H, Finzi A, Xiang SH, Wang L, Princiotto A, Pancera M, Courter J, Smith AB, Freire E, Kwong PD, Sodroski J
- PMC Link #: PMC2738180
Transitions to and from the CD4 bound conformation are modulated by a single residue change in the human immunodeficiency virus type 1 gp120 inner domain
Transitions to and from the CD4-bound conformation are modulated by a single-residue change in the human immunodeficiency virus type 1 gp120 inner domain. J. Virol. 2009;83(17):8364-78 doi: 10.1128/JVI.00594-09
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