A V3 Loop-Dependent gp120 Element Disrupted by CD4 Binding Stabilizes the Human Immunodeficiency Virus Envelope Glycoprotein Trimer

• DOI: 10.1128/jvi.02587-09
• Publication Date: 2010-01-21T02:09:21Z
• Authors: Shi-Hua Xiang; Andrés Finzi; Beatriz Pacheco; Kevin Alexander; Wen Yuan; Carlo Rizzuto; Chih-Chin Huang; Peter D. Kwong; Joseph Sodroski
• Keywords: Trimer; V3 loop

ABSTRACT Human immunodeficiency virus (HIV-1) entry into cells is mediated by a trimeric complex consisting of noncovalently associated gp120 (exterior) and gp41 (transmembrane) envelope glycoproteins. The binding to receptors on the target cell alters gp120-gp41 relationship activates membrane-fusing capacity gp41. Interaction with primary receptor, CD4, results in exposure third variable (V3) loop, which contributes CCR5 or CXCR4 chemokine receptors. We show here that insertions V3 stem polar substitutions conserved hydrophobic patch near tip result decreased association (in unliganded state) receptor CD4-bound state). Subunit syncytium-forming ability glycoproteins from HIV-1 isolates were disrupted more changes than those laboratory-adapted Changes β2, β19, β20, β21 strands, evidence suggests are proximal loop gp120, also resulted association. Thus, element composed adjacent beta strands quaternary interactions stabilize trimer. CD4 dismantles this element, altering rendering available for binding.