Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer. Nat Commun 2018;9(1):1956 doi: 10.1038/s41467-018-04272-y
Scientific Publications
- PMID: 29769533
- Title: Structure of a cleavage independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer
- 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.
- Date: 2018-08-16
- Year: 2018
- Journal: Nat Commun
- PMID Author: Sarkar A, Bale S, Behrens AJ, Kumar S, Sharma SK, de Val N, Pallesen J, Irimia A, Diwanji DC, Stanfield RL, Ward AB, Crispin M, Wyatt RT, Wilson IA
- PMC Link #: PMC5955915
- IAVI Topics: HIV Immunogen Design
Structure of a cleavage independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer
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