6CH9

Crystal structure of a natively-glycosylated B41 SOSIP.664 HIV-1 Envelope Trimer in complex with the broadly-neutralizing antibodies BG18 and 35O22

Summary for 6CH9

• Entry DOI: 10.2210/pdb6ch9/pdb
• Descriptor: Envelope glycoprotein gp41, alpha-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (14 entities in total)
• Functional Keywords: env glycoprotein, broadly neutralizing antibodies, immune system
• Biological source: Human immunodeficiency virus 1; More
• Total number of polymer chains: 6
• Total formula weight: 184637.52

Authors

Barnes, C.O.,Bjorkman, P.J. (deposition date: 2018-02-22, release date: 2018-05-02, Last modification date: 2024-11-06)

Primary citation

Barnes, C.O.,Gristick, H.B.,Freund, N.T.,Escolano, A.,Lyubimov, A.Y.,Hartweger, H.,West, A.P.,Cohen, A.E.,Nussenzweig, M.C.,Bjorkman, P.J.
Structural characterization of a highly-potent V3-glycan broadly neutralizing antibody bound to natively-glycosylated HIV-1 envelope.
Nat Commun, 9:1251-1251, 2018

PubMed 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/N332 glycan-targeting bNAb reported to date. Our structures show conserved contacts mediated by common D gene-encoded residues with the N332 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 N392 and N386 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/N332 bNAbs therapeutically and targeting their epitope for immunogen design.

PubMed: 29593217
DOI: 10.1038/s41467-018-03632-y

Experimental method

X-RAY DIFFRACTION (4.85 Å)