Details

Autor(en) / Beteiligte

• Sarkar, Anita
• Bale, Shridhar
• Behrens, Anna-Janina
• Kumar, Sonu
• Sharma, Shailendra Kumar
• de Val, Natalia
• Pallesen, Jesper
• Irimia, Adriana
• Diwanji, Devan C
• Stanfield, Robyn L
• Ward, Andrew B
• Crispin, Max
• Wyatt, Richard T
• Wilson, Ian A

Titel

Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer

Ist Teil von

• Nature communications, 2018-05, Vol.9 (1), p.1956-14, Article 1956

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.