PDBsum entry 4gmt

Immune system

PDB id: 4gmt

Contents

Protein chains

213 a.a.

213 a.a.

Ligands

NAG-NAG

SO4 ×2

NAG

Waters ×44

PDB id:

4gmt

Name:

Immune system

Title:

Crystal structure of heterosubtypic fab s139/1

Structure:

Fab s139/1 light chain. Chain: l, m. Engineered: yes. Fab s139/1 heavy chain. Chain: h, i. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Strain: s139/1. Expressed in: trichoplusia ni. Expression_system_taxid: 7111.

Resolution:

2.05Å R-factor: 0.160 R-free: 0.209

Authors:

P.S.Lee,D.C.Ekiert,I.A.Wilson

Key ref:

P.S.Lee et al. (2012). Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity. Proc Natl Acad Sci U S A, 109, 17040-17045. PubMed id: 23027945

Date:

16-Aug-12 Release date: 03-Oct-12

Protein chains

No UniProt id for this chain

Struc: 213 a.a.

Protein chains

No UniProt id for this chain

Struc: 213 a.a.

Proc Natl Acad Sci U S A 109:17040-17045 (2012)

PubMed id: 23027945

Heterosubtypic antibody recognition of the influenza virus hemagglutinin receptor binding site enhanced by avidity.

P.S.Lee, R.Yoshida, D.C.Ekiert, N.Sakai, Y.Suzuki, A.Takada, I.A.Wilson.

ABSTRACT

Continual and rapid mutation of seasonal influenza viruses by antigenic drift necessitates the almost annual reformulation of flu vaccines, which may offer little protection if the match to the dominant circulating strain is poor. S139/1 is a cross-reactive antibody that neutralizes multiple HA strains and subtypes, including those from H1N1 and H3N2 viruses that currently infect humans. The crystal structure of the S139/1 Fab in complex with the HA from the A/Victoria/3/1975 (H3N2) virus reveals that the antibody targets highly conserved residues in the receptor binding site and contacts antigenic sites A, B, and D. Binding and plaque reduction assays show that the monovalent Fab alone can protect against H3 strains, but the enhanced avidity from binding of bivalent IgG increases the breadth of neutralization to additional strains from the H1, H2, H13, and H16 subtypes. Thus, antibodies making relatively low affinity Fab interactions with the receptor binding site can have significant antiviral activity when enhanced by avidity through bivalent interactions of the IgG, thereby extending the breadth of binding and neutralization to highly divergent influenza virus strains and subtypes.