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Structural basis for membrane anchoring of HIV-1 envelope spike

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Science  08 Jul 2016:
Vol. 353, Issue 6295, pp. 172-175
DOI: 10.1126/science.aaf7066

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Env's transmembrane domain revealed

HIV-1's envelope protein (Env) spans the viral membrane and grants the virus entry into host cells. Env is also the sole protein of HIV-1 that is targeted by antibodies, making it a key target for vaccine design. Dev et al. used nuclear magnetic resonance to determine an atomic-level structure of the membrane-spanning region of Env in a lipid bicelle. Env's transmembrane domain forms a well-ordered trimer, which includes a stabilizing C-terminal hydrophilic core. Disrupting this core alters the sensitivity of Env to broadly neutralizing antibodies, suggesting the potential importance of this region to vaccine design.

Science, this issue p. 172

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.

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