|Title||Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer.|
|Publication Type||Journal Article|
|Year of Publication||2018|
|Authors||Sarkar A, Bale S, Behrens A-J, Kumar S, Sharma SKumar, de Val N, Pallesen J, Irimia A, Diwanji DC, Stanfield RL, Ward AB, Crispin M, Wyatt RT, Wilson IA|
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.
|Alternate Journal||Nat Commun|
|PubMed Central ID||PMC5955915|
|Grant List||P01 AI104722 / AI / NIAID NIH HHS / United States |
R01 AI084817 / AI / NIAID NIH HHS / United States
R56 AI084817 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer.