EMD-28619

Single-particle
2.7 Å
EMD-28619 Deposition: 19/10/2022
Map released: 27/09/2023
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-28619

Cryo-EM structure of HIV-1 BG505 DS-SOSIP ENV trimer bound to VRC34.01-MM28 FAB

EMD-28619

Single-particle
2.7 Å
EMD-28619 Deposition: 19/10/2022
Map released: 27/09/2023
Last modified: 13/11/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Human immunodeficiency virus 1, Homo sapiens
Sample: BG505 DS-SOSIP VRC34.01-MM28 FAB COMPLEX
Fitted models: 8euw (Avg. Q-score: 0.553)

Deposition Authors: Pletnev S, Kwong P
Antibody-directed evolution reveals a mechanism for enhanced neutralization at the HIV-1 fusion peptide site.
PUBMED: 37989731
DOI: doi:10.1038/s41467-023-42098-5
ISSN: 2041-1723
Abstract:
The HIV-1 fusion peptide (FP) represents a promising vaccine target, but global FP sequence diversity among circulating strains has limited anti-FP antibodies to ~60% neutralization breadth. Here we evolve the FP-targeting antibody VRC34.01 in vitro to enhance FP-neutralization using site saturation mutagenesis and yeast display. Successive rounds of directed evolution by iterative selection of antibodies for binding to resistant HIV-1 strains establish a variant, VRC34.01_mm28, as a best-in-class antibody with 10-fold enhanced potency compared to the template antibody and ~80% breadth on a cross-clade 208-strain neutralization panel. Structural analyses demonstrate that the improved paratope expands the FP binding groove to accommodate diverse FP sequences of different lengths while also recognizing the HIV-1 Env backbone. These data reveal critical antibody features for enhanced neutralization breadth and potency against the FP site of vulnerability and accelerate clinical development of broad HIV-1 FP-targeting vaccines and therapeutics.