PDBsum entry 5i8c

Immune system

PDB id: 5i8c

Contents

Protein chains

223 a.a.

212 a.a.

Ligands

ALA-VAL-GLY-ILE-GLY-ALA-VAL-PHE

Waters ×759

PDB id:

5i8c

Name:

Immune system

Title:

Crystal structure of HIV-1 clade a bg505 fusion peptide (residue 512- 520) in complex with broadly neutralizing antibody vrc34.01 fab

Structure:

Vrc34.01 fab heavy chain. Chain: a. Engineered: yes. Vrc34.01 fab light chain. Chain: b. Engineered: yes. HIV-1 clade a bg505 fusion peptide (residue 512-520). Chain: c. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ighg1. Expressed in: homo sapiens. Expression_system_taxid: 9606. Synthetic: yes. Human immunodeficiency virus 1. Organism_taxid: 11676

Resolution:

1.54Å R-factor: 0.161 R-free: 0.182

Authors:

K.Xu,T.Zhou,K.Liu,P.D.Kwong

Key ref:

R.Kong et al. (2016). Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody. Science, 352, 828-833. PubMed id: 27174988 DOI: 10.1126/science.aae0474

Date:

18-Feb-16 Release date: 25-May-16

Protein chain

No UniProt id for this chain

Struc: 223 a.a.

Protein chain

No UniProt id for this chain

Struc: 212 a.a.

DOI no: 10.1126/science.aae0474

Science 352:828-833 (2016)

PubMed id: 27174988

Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody.

R.Kong, K.Xu, T.Zhou, P.Acharya, T.Lemmin, K.Liu, G.Ozorowski, C.Soto, J.D.Taft, R.T.Bailer, E.M.Cale, L.Chen, C.W.Choi, G.Y.Chuang, N.A.Doria-Rose, A.Druz, I.S.Georgiev, J.Gorman, J.Huang, M.G.Joyce, M.K.Louder, X.Ma, K.McKee, S.O'Dell, M.Pancera, Y.Yang, S.C.Blanchard, W.Mothes, D.R.Burton, W.C.Koff, M.Connors, A.B.Ward, P.D.Kwong, J.R.Mascola.

ABSTRACT

The HIV-1 fusion peptide, comprising 15 to 20 hydrophobic residues at the N terminus of the Env-gp41 subunit, is a critical component of the virus-cell entry machinery. Here, we report the identification of a neutralizing antibody, N123-VRC34.01, which targets the fusion peptide and blocks viral entry by inhibiting conformational changes in gp120 and gp41 subunits of Env required for entry. Crystal structures of N123-VRC34.01 liganded to the fusion peptide, and to the full Env trimer, revealed an epitope consisting of the N-terminal eight residues of the gp41 fusion peptide and glycan N88 of gp120, and molecular dynamics showed that the N-terminal portion of the fusion peptide can be solvent-exposed. These results reveal the fusion peptide to be a neutralizing antibody epitope and thus a target for vaccine design.