5V8M

BG505 SOSIP.664 trimer in complex with broadly neutralizing HIV antibody 3BNC117

Summary for 5V8M

• Entry DOI: 10.2210/pdb5v8m/pdb
• EMDB information: 8644
• Descriptor: gp120, 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, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total)
• Functional Keywords: hiv, broadly neutralizing antibody, 3bnc117, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 12
• Total formula weight: 386622.31

Authors

Lee, J.H.,Cottrell, C.A.,Ward, A.B. (deposition date: 2017-03-22, release date: 2017-05-03, Last modification date: 2024-11-06)

Primary citation

Lee, J.H.,Andrabi, R.,Su, C.Y.,Yasmeen, A.,Julien, J.P.,Kong, L.,Wu, N.C.,McBride, R.,Sok, D.,Pauthner, M.,Cottrell, C.A.,Nieusma, T.,Blattner, C.,Paulson, J.C.,Klasse, P.J.,Wilson, I.A.,Burton, D.R.,Ward, A.B.
A Broadly Neutralizing Antibody Targets the Dynamic HIV Envelope Trimer Apex via a Long, Rigidified, and Anionic beta-Hairpin Structure.
Immunity, 46:690-702, 2017

PubMed Abstract: Broadly neutralizing antibodies (bnAbs) to HIV delineate vaccine targets and are prophylactic and therapeutic agents. Some of the most potent bnAbs target a quaternary epitope at the apex of the surface HIV envelope (Env) trimer. Using cryo-electron microscopy, we solved the atomic structure of an apex bnAb, PGT145, in complex with Env. We showed that the long anionic HCDR3 of PGT145 penetrated between glycans at the trimer 3-fold axis, to contact peptide residues from all three Env protomers, and thus explains its highly trimer-specific nature. Somatic hypermutation in the other CDRs of PGT145 were crucially involved in stabilizing the structure of the HCDR3, similar to bovine antibodies, to aid in recognition of a cluster of conserved basic residues hypothesized to facilitate trimer disassembly during viral entry. Overall, the findings exemplify the creative solutions that the human immune system can evolve to recognize a conserved motif buried under a canopy of glycans.

PubMed: 28423342
DOI: 10.1016/j.immuni.2017.03.017

Experimental method

ELECTRON MICROSCOPY (4.4 Å)