PDBsum entry 4fqc

Immune system

PDB id: 4fqc

Contents

Protein chains

227 a.a.

206 a.a.

Ligands

NAG-NAG-BMA-MAN-NAG-GAL-SIA-MAN-NAG-FUC

TAM

Waters ×146

PDB id:

4fqc

Name:

Immune system

Title:

Crystal structure of pgt121 fab bound to a complex-type sialylated n- glycan

Structure:

Fab heavy chain. Chain: h. Engineered: yes. Fab light chain. Chain: l. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293-6e.

Resolution:

2.40Å R-factor: 0.203 R-free: 0.249

Authors:

L.Scharf,P.J.Bjorkman

Key ref:

H.Mouquet et al. (2012). Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proc Natl Acad Sci U S A, 109, E3268. PubMed id: 23115339

Date:

25-Jun-12 Release date: 14-Nov-12

Protein chain

No UniProt id for this chain

Struc: 227 a.a.

Protein chain

No UniProt id for this chain

Struc: 206 a.a.

Proc Natl Acad Sci U S A 109:E3268 (2012)

PubMed id: 23115339

Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies.

H.Mouquet, L.Scharf, Z.Euler, Y.Liu, C.Eden, J.F.Scheid, A.Halper-Stromberg, P.N.Gnanapragasam, D.I.Spencer, M.S.Seaman, H.Schuitemaker, T.Feizi, M.C.Nussenzweig, P.J.Bjorkman.

ABSTRACT

Broadly neutralizing HIV antibodies (bNAbs) can recognize carbohydrate-dependent epitopes on gp120. In contrast to previously characterized glycan-dependent bNAbs that recognize high-mannose N-glycans, PGT121 binds complex-type N-glycans in glycan microarrays. We isolated the B-cell clone encoding PGT121, which segregates into PGT121-like and 10-1074-like groups distinguished by sequence, binding affinity, carbohydrate recognition, and neutralizing activity. Group 10-1074 exhibits remarkable potency and breadth but no detectable binding to protein-free glycans. Crystal structures of unliganded PGT121, 10-1074, and their likely germ-line precursor reveal that differential carbohydrate recognition maps to a cleft between complementarity determining region (CDR)H2 and CDRH3. This cleft was occupied by a complex-type N-glycan in a "liganded" PGT121 structure. Swapping glycan contact residues between PGT121 and 10-1074 confirmed their importance for neutralization. Although PGT121 binds complex-type N-glycans, PGT121 recognized high-mannose-only HIV envelopes in isolation and on virions. As HIV envelopes exhibit varying proportions of high-mannose- and complex-type N-glycans, these results suggest promiscuous carbohydrate interactions, an advantageous adaptation ensuring neutralization of all viruses within a given strain.