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Structural basis for membrane anchoring of HIV-1 envelope spike.

ABSTRACT: HIV-1 envelope spike (Env) is a type I membrane protein that mediates viral entry. We used nuclear magnetic resonance to determine an atomic structure of the transmembrane (TM) domain of HIV-1 Env reconstituted in bicelles that mimic a lipid bilayer. The TM forms a well-ordered trimer that protects a conserved membrane-embedded arginine. An amino-terminal coiled-coil and a carboxyl-terminal hydrophilic core stabilize the trimer. Individual mutations of conserved residues did not disrupt the TM trimer and minimally affected membrane fusion and infectivity. Major changes in the hydrophilic core, however, altered the antibody sensitivity of Env. These results show how a TM domain anchors, stabilizes, and modulates a viral envelope spike and suggest that its influence on Env conformation is an important consideration for HIV-1 immunogen design.

SUBMITTER: Dev J

PROVIDER: S-EPMC5085267 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Structural basis for membrane anchoring of HIV-1 envelope spike.

Dev Jyoti J Park Donghyun D Fu Qingshan Q Chen Jia J Ha Heather Jiwon HJ Ghantous Fadi F Herrmann Tobias T Chang Weiting W Liu Zhijun Z Frey Gary G Seaman Michael S MS Chen Bing B Chou James J JJ

Science (New York, N.Y.) 20160623 6295

HIV-1 envelope spike (Env) is a type I membrane protein that mediates viral entry. We used nuclear magnetic resonance to determine an atomic structure of the transmembrane (TM) domain of HIV-1 Env reconstituted in bicelles that mimic a lipid bilayer. The TM forms a well-ordered trimer that protects a conserved membrane-embedded arginine. An amino-terminal coiled-coil and a carboxyl-terminal hydrophilic core stabilize the trimer. Individual mutations of conserved residues did not disrupt the TM t ...[more]

PMID: 27338706

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