Tilted, Uninterrupted, Monomeric HIV-1 Gp41 Transmembrane Helix from Residual Dipolar Couplings

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2017 Dec 27

PMID 29277995

Citations 29

Authors

Sai Chaitanya Chiliveri

John M Louis

Rodolfo Ghirlando

James L Baber

Ad Bax

Affiliations

Soon will be listed here.

Abstract

Cryo-electron microscopy and X-ray crystallography have shown that the pre- and postfusion states of the HIV-1 gp41 viral coat protein, although very different from one another, each adopt C symmetric structures. A stable homotrimeric structure for the transmembrane domain (TM) also was modeled and supported by experimental data. For a C symmetric structure, alignment in an anisotropic medium must be axially symmetric, with the unique axis of the alignment tensor coinciding with the C axis. However, NMR residual dipolar couplings (RDCs) measured under three different alignment conditions were found to be incompatible with C symmetry. Subsequent measurements by paramagnetic relaxation enhancement, analytical ultracentrifugation, and DEER EPR, indicate that the transmembrane domain is monomeric. N NMR relaxation data and RDCs show that TM is highly ordered and uninterrupted for a total length of 32 residues, extending well into the membrane proximal external region.

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