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TitleA Broadly Neutralizing Antibody Targets the Dynamic HIV Envelope Trimer Apex via a Long, Rigidified, and Anionic β-Hairpin Structure.
Journal, issue, pagesImmunity, Vol. 46, Issue 4, Page 690-702, Year 2017
Publish dateApr 18, 2017
AuthorsJeong 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 AbstractBroadly 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 linksImmunity / PubMed:28423342 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.9 - 4.4 Å
Structure data

8643

5v8l

EMDB-8643, PDB-5v8l:
BG505 SOSIP.664 trimer in complex with broadly neutralizing HIV antibodies 3BNC117 and PGT145
Method: EM (single particle) / Resolution: 4.3 Å

8644

5v8m

EMDB-8644, PDB-5v8m:
BG505 SOSIP.664 trimer in complex with broadly neutralizing HIV antibody 3BNC117
Method: EM (single particle) / Resolution: 4.4 Å

PDB-5uy3:
Crystal structure of human Fab PGT144, a broadly reactive and potent HIV-1 neutralizing antibody
Method: X-RAY DIFFRACTION / Resolution: 2.9 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • human immunodeficiency virus 1
  • homo sapiens (human)
KeywordsIMMUNE SYSTEM / Antibody / HIV Env glycoprotein / VIRAL PROTEIN/IMMUNE SYSTEM / HIV / broadly neutralizing antibody / PGT145 / VIRAL PROTEIN-IMMUNE SYSTEM complex / 3BNC117

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