Abstract

Broadly neutralizing antibodies (bNAbs) isolated from HIV-1-infected individuals inform HIV-1 vaccine design efforts. Developing bNAbs with increased efficacy requires understanding how antibodies interact with the native oligomannose and complex-type N-glycan shield that hides most protein epitopes on HIV-1 envelope (Env). Here we present crystal structures, including a 3.8-Å X-ray free electron laser dataset, of natively glycosylated Env trimers complexed with BG18, the most potent V3/N332gp120 glycan-targeting bNAb reported to date. Our structures show conserved contacts mediated by common D gene-encoded residues with the N332gp120 glycan and the gp120 GDIR peptide motif, but a distinct Env-binding orientation relative to PGT121/10-1074 bNAbs. BG18’s binding orientation provides additional contacts with N392gp120 and N386gp120 glycans near the V3-loop base and engages protein components of the V1-loop. The BG18-natively-glycosylated Env structures facilitate understanding of bNAb–glycan interactions critical for using V3/N332gp120 bNAbs therapeutically and targeting their epitope for immunogen design.

Details

Title
Structural characterization of a highly-potent V3-glycan broadly neutralizing antibody bound to natively-glycosylated HIV-1 envelope
Author
Barnes, Christopher O 1 ; Gristick, Harry B 1 ; Freund, Natalia T 2 ; Escolano, Amelia 3 ; Lyubimov, Artem Y 4 ; Hartweger, Harald 3 ; West, Anthony P, Jr 1 ; Cohen, Aina E 4 ; Nussenzweig, Michel C 5 ; Bjorkman, Pamela J 1 

 Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA 
 Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA; Department of Clinical Immunology and Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel 
 Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA 
 Stanford Synchrotron Radiation Lightsource, Menlo Park, CA, USA 
 Laboratory of Molecular Immunology, The Rockefeller University, New York, NY, USA; Howard Hughes Medical Institute, The Rockefeller University, New York, NY, USA 
Pages
1-12
Publication year
2018
Publication date
Mar 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2019432847
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.