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Structure paper

TitleStructural basis of broad HIV neutralization by a vaccine-induced cow antibody.
Journal, issue, pagesSci Adv, Vol. 6, Issue 22, Page eaba0468, Year 2020
Publish dateMay 27, 2020
AuthorsRobyn L Stanfield / Zachary T Berndsen / Ruiqi Huang / Devin Sok / Gabrielle Warner / Jonathan L Torres / Dennis R Burton / Andrew B Ward / Ian A Wilson / Vaughn V Smider /
PubMed AbstractPotent broadly neutralizing antibodies (bnAbs) to HIV have been very challenging to elicit by vaccination in wild-type animals. Here, by x-ray crystallography, cryo-electron microscopy, and site- ...Potent broadly neutralizing antibodies (bnAbs) to HIV have been very challenging to elicit by vaccination in wild-type animals. Here, by x-ray crystallography, cryo-electron microscopy, and site-directed mutagenesis, we structurally and functionally elucidate the mode of binding of a potent bnAb (NC-Cow1) elicited in cows by immunization with the HIV envelope (Env) trimer BG505 SOSIP.664. The exceptionally long (60 residues) third complementarity-determining region of the heavy chain (CDR H3) of NC-Cow1 forms a mini domain (knob) on an extended stalk that navigates through the dense glycan shield on Env to target a small footprint on the gp120 CD4 receptor binding site with no contact of the other CDRs to the rest of the Env trimer. These findings illustrate, in molecular detail, how an unusual vaccine-induced cow bnAb to HIV Env can neutralize with high potency and breadth.
External linksSci Adv / PubMed:32518821 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.1 - 4.5 Å
Structure data

20500

6pw6

EMDB-20500, PDB-6pw6:
The HIV-1 Envelope Glycoprotein Clone BG505 SOSIP.664 in Complex with Three Copies of the Bovine Broadly Neutralizing Antibody, NC-Cow1, Fragment Antigen Binding Domain
Method: EM (single particle) / Resolution: 4.5 Å

PDB-6oo0:
Crystal structure of bovine Fab NC-Cow1
Method: X-RAY DIFFRACTION / Resolution: 2.1 Å

PDB-6opa:
Crystal structure of bovine Fab NC-Cow1 in complex with HIV-1 BG505 SOSIP.664, and human Fabs 35022 and PGT128
Method: X-RAY DIFFRACTION / Resolution: 4.084 Å

Chemicals

ChemComp-MPD:
(4S)-2-METHYL-2,4-PENTANEDIOL / precipitant*YM / 2-Methyl-2,4-pentanediol

ChemComp-HOH:
WATER / Water

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

Source
  • human immunodeficiency virus 1
  • bos taurus (cattle)
  • homo sapiens (human)
KeywordsIMMUNE SYSTEM / HIV-1 broadly neutralizing antibody / VIRAL PROTEIN-Immune System complex / VIRAL PROTEIN/IMMUNE SYSTEM / HIV Vaccine / Cow Antibody

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