PDBsum entry 6pw6

Viral protein/immune system

PDB id: 6pw6

Contents

Protein chains

439 a.a.

126 a.a.

49 a.a.

Ligands

NAG-NAG ×24

NAG-NAG-BMA-MAN ×6

NAG ×36

PDB id:

6pw6

Name:

Viral protein/immune system

Title:

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

Structure:

Envelope glycoprotein gp120. Chain: a, c, e. Engineered: yes. Envelope glycoprotein gp41. Chain: b, d, f. Engineered: yes. Broadly neutralizing antibody nc-cow1 heavy chain. Chain: g, h, i. Fragment: fab.

Source:

Human immunodeficiency virus 1. HIV-1. Organism_taxid: 11676. Gene: env. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293f. Bos taurus. Bovine.

Authors:

Z.T.Berndsen,A.B.Ward

Key ref:

R.L.Stanfield et al. (2020). Structural basis of broad HIV neutralization by a vaccine-induced cow antibody. Sci Adv, 6, eaba0468. PubMed id: 32518821 DOI: 10.1126/sciadv.aba0468

Date:

22-Jul-19 Release date: 24-Jun-20

Protein chains

Q2N0S6  (Q2N0S6_HV1) -  Envelope glycoprotein gp160 from Human immunodeficiency virus type 1

Seq: 860 a.a.

Struc: 439 a.a.*

Protein chains

Q2N0S6  (Q2N0S6_HV1) -  Envelope glycoprotein gp160 from Human immunodeficiency virus type 1

Seq: 860 a.a.

Struc: 126 a.a.*

Protein chains

No UniProt id for this chain

Struc: 49 a.a.

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1126/sciadv.aba0468

Sci Adv 6:eaba0468 (2020)

PubMed id: 32518821

Structural basis of broad HIV neutralization by a vaccine-induced cow antibody.

R.L.Stanfield, Z.T.Berndsen, R.Huang, D.Sok, G.Warner, J.L.Torres, D.R.Burton, A.B.Ward, I.A.Wilson, V.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-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.