6OKP

B41 SOSIP.664 in complex with the silent-face antibody SF12 and V3-targeting antibody 10-1074

Summary for 6OKP

• Entry DOI: 10.2210/pdb6okp/pdb
• EMDB information: 20100 20101
• Descriptor: Envelope glycoprotein gp41, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 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: hiv-1 broadly-neutralizing antibody, env trimer structure, silent face, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 14
• Total formula weight: 453207.76

Authors

Barnes, C.O.,Bjorkman, P.J. (deposition date: 2019-04-14, release date: 2019-06-05, Last modification date: 2024-10-16)

Primary citation

Schoofs, T.,Barnes, C.O.,Suh-Toma, N.,Golijanin, J.,Schommers, P.,Gruell, H.,West Jr., A.P.,Bach, F.,Lee, Y.E.,Nogueira, L.,Georgiev, I.S.,Bailer, R.T.,Czartoski, J.,Mascola, J.R.,Seaman, M.S.,McElrath, M.J.,Doria-Rose, N.A.,Klein, F.,Nussenzweig, M.C.,Bjorkman, P.J.
Broad and Potent Neutralizing Antibodies Recognize the Silent Face of the HIV Envelope.
Immunity, 50:1513-, 2019

PubMed Abstract: Broadly neutralizing antibodies (bNAbs) against HIV-1 envelope (Env) inform vaccine design and are potential therapeutic agents. We identified SF12 and related bNAbs with up to 62% neutralization breadth from an HIV-infected donor. SF12 recognized a glycan-dominated epitope on Env's silent face and was potent against clade AE viruses, which are poorly covered by V3-glycan bNAbs. A 3.3Å cryo-EM structure of a SF12-Env trimer complex showed additional contacts to Env protein residues by SF12 compared with VRC-PG05, the only other known donor-derived silentface antibody, explaining SF12's increased neutralization breadth, potency, and resistance to Env mutation routes. Asymmetric binding of SF12 was associated with distinct N-glycan conformations across Env protomers, demonstrating intra-Env glycan heterogeneity. Administrating SF12 to HIV-1-infected humanized mice suppressed viremia and selected for viruses lacking the N448 glycan. Effective bNAbs can therefore be raised against HIV-1 Env's silent face, suggesting their potential for HIV-1 prevention, therapy, and vaccine development.

PubMed: 31126879
DOI: 10.1016/j.immuni.2019.04.014

Experimental method

ELECTRON MICROSCOPY (3.28 Å)