Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer
Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer
Furin cleavage of the HIV envelope glycoprotein is an essential step for cell entry that enables formation of well-folded, native-like glycosylated trimers, releases constraints on the fusion peptide, and limits enzymatic processing of the N-glycan shield. Here, we show that a cleavage-independent, stabilized, soluble Env trimer mimic (BG505 NFL.664) exhibits a "closed-form", native-like, prefusion conformation akin to furin-cleaved Env trimers. The crystal structure of BG505 NFL.664 at 3.39 Å resolution with two potent bNAbs also identifies the full epitopes of PGV19 and PGT122 that target the receptor binding site and N332 supersite, respectively. Quantitative site-specific analysis of the glycan shield reveals that native-like glycan processing is maintained despite furin-independent maturation in the secretory pathway. Thus, cleavage-independent NFL Env trimers exhibit quaternary protein and carbohydrate structures similar to the native viral spike that further validate their potential as vaccine immunogen candidates.
1-14
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Crispin, Max
cd980957-0943-4b89-b2b2-710f01f33bc9
Crispin, Max
(2018)
Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer.
Nature Communications, , [1956].
(doi:10.1038/s41467-018-04272-y).
Abstract
Furin cleavage of the HIV envelope glycoprotein is an essential step for cell entry that enables formation of well-folded, native-like glycosylated trimers, releases constraints on the fusion peptide, and limits enzymatic processing of the N-glycan shield. Here, we show that a cleavage-independent, stabilized, soluble Env trimer mimic (BG505 NFL.664) exhibits a "closed-form", native-like, prefusion conformation akin to furin-cleaved Env trimers. The crystal structure of BG505 NFL.664 at 3.39 Å resolution with two potent bNAbs also identifies the full epitopes of PGV19 and PGT122 that target the receptor binding site and N332 supersite, respectively. Quantitative site-specific analysis of the glycan shield reveals that native-like glycan processing is maintained despite furin-independent maturation in the secretory pathway. Thus, cleavage-independent NFL Env trimers exhibit quaternary protein and carbohydrate structures similar to the native viral spike that further validate their potential as vaccine immunogen candidates.
Text
Sarkar_NatComms_2018
- Version of Record
More information
Accepted/In Press date: 13 April 2018
e-pub ahead of print date: 16 May 2018
Identifiers
Local EPrints ID: 421294
URI: http://eprints.soton.ac.uk/id/eprint/421294
PURE UUID: e35ca5e3-fd37-4835-9047-f22394029f47
Catalogue record
Date deposited: 31 May 2018 16:30
Last modified: 16 Mar 2024 04:30
Export record
Altmetrics
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
