+Search query
-Structure paper
Title | A Broadly Neutralizing Antibody Targets the Dynamic HIV Envelope Trimer Apex via a Long, Rigidified, and Anionic β-Hairpin Structure. |
---|---|
Journal, issue, pages | Immunity, Vol. 46, Issue 4, Page 690-702, Year 2017 |
Publish date | Apr 18, 2017 |
Authors | Jeong Hyun Lee / Raiees Andrabi / Ching-Yao Su / Anila Yasmeen / Jean-Philippe Julien / Leopold Kong / Nicholas C Wu / Ryan McBride / Devin Sok / Matthias Pauthner / Christopher A Cottrell / Travis Nieusma / Claudia Blattner / James C Paulson / Per Johan Klasse / Ian A Wilson / Dennis R Burton / Andrew B Ward / |
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 ...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. |
External links | Immunity / PubMed:28423342 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 2.9 - 4.4 Å |
Structure data | EMDB-8643, PDB-5v8l: EMDB-8644, PDB-5v8m: PDB-5uy3: |
Chemicals | ChemComp-NAG: |
Source |
|
Keywords | IMMUNE SYSTEM / Antibody / HIV Env glycoprotein / VIRAL PROTEIN/IMMUNE SYSTEM / HIV / broadly neutralizing antibody / PGT145 / VIRAL PROTEIN-IMMUNE SYSTEM complex / 3BNC117 |