AI Article Synopsis

  • Furin cleavage of HIV envelope proteins is crucial for allowing the virus to enter cells by forming stable, well-structured trimers and protecting against enzymatic breakdown.
  • A stable, cleavage-independent Env trimer mimic, named BG505 NFL.664, retains a native-like structure similar to furin-cleaved forms, making it a valuable model for study.
  • Analysis of BG505 NFL.664 reveals it has intact glycan shielding and maintains essential protein structures, highlighting its potential use as a candidate for developing effective vaccines against HIV.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955915PMC
http://dx.doi.org/10.1038/s41467-018-04272-yDOI Listing

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