7MXE

Ab1245 Fab in complex with BG505 SOSIP.664 and 8ANC195 Fab

Summary for 7MXE

• Entry DOI: 10.2210/pdb7mxe/pdb
• EMDB information: 24072
• Descriptor: 8ANC195 G52K5 Fab heavy chain, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)]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)-[alpha-D-mannopyranose-(1-6)]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: viral protein-immune system complex, non-neutralizing, antiviral protein, antiviral protein-viral protein complex, antiviral protein/viral protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 14
• Total formula weight: 440649.06

Authors

Abernathy, M.E.,Bjorkman, P.J. (deposition date: 2021-05-19, release date: 2021-10-27, Last modification date: 2024-10-23)

Primary citation

Abernathy, M.E.,Gristick, H.B.,Vielmetter, J.,Keeffe, J.R.,Gnanapragasam, P.N.P.,Lee, Y.E.,Escolano, A.,Gautam, R.,Seaman, M.S.,Martin, M.A.,Nussenzweig, M.C.,Bjorkman, P.J.
Antibody elicited by HIV-1 immunogen vaccination in macaques displaces Env fusion peptide and destroys a neutralizing epitope.
Npj Vaccines, 6:126-126, 2021

PubMed Abstract: HIV-1 vaccine design aims to develop an immunogen that elicits broadly neutralizing antibodies against a desired epitope, while eliminating responses to off-target regions of HIV-1 Env. We report characterization of Ab1245, an off-target antibody against the Env gp120-gp41 interface, from V3-glycan patch immunogen-primed and boosted macaques. A 3.7 Å cryo-EM structure of an Ab1245-Env complex reveals one Ab1245 Fab binding asymmetrically to Env trimer at the gp120-gp41 interface using its long CDRH3 to mimic regions of gp41. The mimicry includes positioning of a CDRH3 methionine into the gp41 tryptophan clasp, resulting in displacement of the fusion peptide and fusion peptide-proximal region. Despite fusion peptide displacement, Ab1245 is non-neutralizing even at high concentrations, raising the possibility that only two fusion peptides per trimer are required for viral-host membrane fusion. These structural analyses facilitate immunogen design to prevent elicitation of Ab1245-like antibodies that block neutralizing antibodies against the fusion peptide.

PubMed: 34697307
DOI: 10.1038/s41541-021-00387-4

Experimental method

ELECTRON MICROSCOPY (3.7 Å)