A Broadly Neutralizing Antibody Targets the Dynamic HIV Envelope Trimer Apex via a Long, Rigidified, and Anionic β-Hairpin Structure
作者： Jeong Hyun Lee , Raiees Andrabi , Ching-Yao Su , Anila Yasmeen , Jean-Philippe Julien
DOI: 10.1016/J.IMMUNI.2017.03.017
关键词:
摘要: Summary Broadly neutralizing antibodies (bnAbs) to HIV delineate vaccine targets and are prophylactic therapeutic agents. Some of the most potent bnAbs target a quaternary epitope at apex surface envelope (Env) trimer. Using cryo-electron microscopy, we solved atomic structure an bnAb, PGT145, in complex with Env. We showed that long anionic HCDR3 PGT145 penetrated between glycans trimer 3-fold axis, contact peptide residues from all three Env protomers, thus explains its highly trimer-specific nature. Somatic hypermutation other CDRs were crucially involved stabilizing HCDR3, similar bovine antibodies, aid recognition cluster conserved basic hypothesized facilitate disassembly during viral entry. Overall, findings exemplify creative solutions human immune system can evolve recognize motif buried under canopy glycans.
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