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

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

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.

Furin, Glycan, Glycosylation, Human immunodeficiency virus, Neutralizing antibodies, Oligosaccharides, Structure, Vaccines
0022-538X
Behrens, Anna Janina
ed584c40-79cb-4de9-bb9c-bd68c71d6a68
Harvey, David J.
8bb24417-3852-4b1f-827b-0d5d2c176744
Milne, Emilia
55b6b4b7-18a2-42d9-bd18-c8bdb8dd2875
Cupo, Albert
aa9f476e-3296-4118-9231-0edc774b8335
Kumar, Abhinav
22f8d17d-11d5-4c38-8b5c-ea479bd60bad
Zitzmann, Nicole
f20f9920-574a-4aac-a86f-1625dd60125c
Struwe, Weston B.
16a348b1-3921-4a2d-b5fb-d341fccea65f
Moore, John P.
3c26226c-c036-48db-bbd1-828a86b29697
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Behrens, Anna Janina
ed584c40-79cb-4de9-bb9c-bd68c71d6a68
Harvey, David J.
8bb24417-3852-4b1f-827b-0d5d2c176744
Milne, Emilia
55b6b4b7-18a2-42d9-bd18-c8bdb8dd2875
Cupo, Albert
aa9f476e-3296-4118-9231-0edc774b8335
Kumar, Abhinav
22f8d17d-11d5-4c38-8b5c-ea479bd60bad
Zitzmann, Nicole
f20f9920-574a-4aac-a86f-1625dd60125c
Struwe, Weston B.
16a348b1-3921-4a2d-b5fb-d341fccea65f
Moore, John P.
3c26226c-c036-48db-bbd1-828a86b29697
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9

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). (doi:10.1128/JVI.01894-16).

Record type: Article

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.

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More information

Accepted/In Press date: 25 October 2016
e-pub ahead of print date: 2 November 2016
Published date: January 2017
Keywords: Furin, Glycan, Glycosylation, Human immunodeficiency virus, Neutralizing antibodies, Oligosaccharides, Structure, Vaccines

Identifiers

Local EPrints ID: 414338
URI: https://eprints.soton.ac.uk/id/eprint/414338
ISSN: 0022-538X
PURE UUID: afebd83a-dbfb-47f8-96bc-750a447299fb
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

Catalogue record

Date deposited: 26 Sep 2017 16:30
Last modified: 14 Mar 2019 01:25

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Contributors

Author: Anna Janina Behrens
Author: David J. Harvey
Author: Emilia Milne
Author: Albert Cupo
Author: Abhinav Kumar
Author: Nicole Zitzmann
Author: Weston B. Struwe
Author: John P. Moore
Author: Max Crispin ORCID iD

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