6okp | pdb_00006okp
B41 SOSIP.664 in complex with the silent-face antibody SF12 and V3-targeting antibody 10-1074
Structural highlights
Publication Abstract from PubMedBroadly 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 3.3A 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 N448gp120 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. Broad and Potent Neutralizing Antibodies Recognize the Silent Face of the HIV Envelope.,Schoofs T, Barnes CO, Suh-Toma N, Golijanin J, Schommers P, Gruell H, West AP Jr, Bach F, Lee YE, Nogueira L, Georgiev IS, Bailer RT, Czartoski J, Mascola JR, Seaman MS, McElrath MJ, Doria-Rose NA, Klein F, Nussenzweig MC, Bjorkman PJ Immunity. 2019 May 14. pii: S1074-7613(19)30194-3. doi:, 10.1016/j.immuni.2019.04.014. PMID:31126879[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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