National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM105826
United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI117675
United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI084817
United States
Citation
Journal: Sci Adv / Year: 2020 Title: Structural basis of broad HIV neutralization by a vaccine-induced cow antibody. Authors: Robyn 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 / Abstract: 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- ...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.
Mass: 22633.688 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Cell line (production host): HEK 293F / Production host: Homo sapiens (human)
#2: Antibody
NC-Cow1heavychain
Mass: 29357.709 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Cell line (production host): HEK 293F / Production host: Homo sapiens (human)
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