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

Summary for 6PW6

• Entry DOI: 10.2210/pdb6pw6/pdb
• EMDB information: 20500
• Descriptor: Envelope glycoprotein gp120, Envelope glycoprotein gp41, Broadly Neutralizing Antibody NC-Cow1 Heavy Chain, ... (6 entities in total)
• Functional Keywords: hiv vaccine, cow antibody, viral protein-immune system complex, viral protein/immune system
• Biological source: Human immunodeficiency virus 1 (HIV-1); More
• Total number of polymer chains: 9
• Total formula weight: 334703.45

Authors

Berndsen, Z.T.,Ward, A.B. (deposition date: 2019-07-22, release date: 2020-06-24, Last modification date: 2024-10-23)

Primary citation

Stanfield, R.L.,Berndsen, Z.T.,Huang, R.,Sok, D.,Warner, G.,Torres, J.L.,Burton, D.R.,Ward, A.B.,Wilson, I.A.,Smider, V.V.
Structural basis of broad HIV neutralization by a vaccine-induced cow antibody.
Sci Adv, 6:eaba0468-eaba0468, 2020

PubMed 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-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.

PubMed: 32518821
DOI: 10.1126/sciadv.aba0468

Experimental method

ELECTRON MICROSCOPY (4.5 Å)