Molecular Architecture of the cleavage- dependent mannose patch on a soluble HIV-1 envelope glycoprotein trimer

Behrens, Anna Janina, Harvey, David J., Milne, Emilia, Cupo, Albert, Kumar, Abhinav, Zitzmann, Nicole, Struwe, Weston B., Moore, John P. and Crispin, Max (2017) Molecular Architecture of the cleavage- dependent mannose patch on a soluble HIV-1 envelope glycoprotein trimer. Journal of Virology, 91 (2), [e01894-16]. (doi:10.1128/JVI.01894-16).

Abstract

The formation of a correctly folded and natively glycosylated HIV-1 viral spike is dependent on protease cleavage of the gp160 precursor protein in the Golgi apparatus. Cleavage induces a compact structure which not only renders the spike capable of fusion but also limits further maturation of its extensive glycosylation. The redirection of the glycosylation pathway to preserve underprocessed oligomannose-type glycans is an important feature in immunogen design, as glycans contribute to or influence the epitopes of numerous broadly neutralizing antibodies. Here we present a quantitative site-specific analysis of a recombinant, trimeric mimic of the native HIV-1 viral spike (BG505 SOSIP.664) compared to the corresponding uncleaved pseudotrimer and the matched gp120 monomer. We present a detailed molecular map of a trimer-associated glycan remodeling that forms a localized subdomain of the native mannose patch. The formation of native trimers is a critical design feature in shaping the glycan epitopes presented on recombinant vaccine candidates.

This record has no associated files available for download.

Contributors

Author: Max Crispin

Download statistics