An allosteric rheostat in HIV-1 gp120 reduces CCR5 stoichiometry required for membrane fusion and overcomes diverse entry limitations.

ABSTRACT: Binding of the human immunodeficiency virus (HIV-1) envelope glycoprotein gp120 to the CCR5 co-receptor reduces constraints on the metastable transmembrane subunit gp41, thereby enabling gp41 refolding, fusion of viral and cellular membranes, and infection. We previously isolated adapted HIV-1(JRCSF) variants that more efficiently use mutant CCR5s, including CCR5(Delta18) lacking the important tyrosine sulfate-containing amino terminus. Effects of mutant CCR5 concentrations on HIV-1 infectivities were highly cooperative, implying that several may be required. However, because wild-type CCR5 efficiently mediates infections at trace concentrations that were difficult to measure accurately, analyses of its cooperativity were not feasible. New HIV-1(JRCSF) variants efficiently use CCR5(HHMH),

SUBMITTER: Platt EJ 

PROVIDER: S-EPMC2704606 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature