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An Asymmetric Opening of HIV-1 Envelope Mediates Antibody-Dependent Cellular Cytotoxicity.

Cell Host Microbe. 2019-04;

AlsahafiNirmin，BakoucheNordine，KazemiMohsen，RichardJonathan，DingShilei，BhattacharyyaSudipta，DasDurba，AnandSai Priya，PrévostJérémie，TolbertWilliam D，LuHong，MedjahedHalima，Gendron-LepageGabrielle，Ortega DelgadoGloria Gabrielle，KirkSharon，MelilloBruno，MothesWalther，SodroskiJoseph，SmithAmos B，KaufmannDaniel E，WuXueling，PazgierMarzena，RouillerIsabelle，FinziAndrés，MunroJam

Products/Services Used	Details	Operation
Codon Optimization	The sequence of full-length clade B HIV-1JRFL Env (Wu et al., 2006) was codon-optimized (GenScript) and cloned into the expression plasmid pcDNA3.1 or PCGGS.	Get A Quote

摘要

The HIV-1 envelope glycoprotein (Env) (gp120-gp41) is the target for neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC). HIV-1 Env is flexible， sampling different conformational states. Before engaging CD4， Env adopts a closed conformation (State 1) that is largely antibody resistant. CD4 binding induces an intermediate state (State 2)， followed by an open conformation (State 3) that is susceptible to engagement by antibodies that recognize otherwise occluded epitopes. We investigate conformational changes in Env that induce ADCC in the presence of a small-molecule CD4-mimetic compound (CD4mc). We uncover an asymmetric Env conformation (State 2A) recognized by antibodies targeting... More