PDBsum entry 3ikc

Immune system

PDB id: 3ikc

Contents

Protein chains

217 a.a. *

221 a.a. *

Ligands

KME-KDO ×2

Metals

_MG ×2

Waters ×333

* Residue conservation analysis

PDB id:

3ikc

Name:

Immune system

Title:

Structure of s67-27 in complex with kdo(2.8)-7-o-methyl-kdo

Structure:

Immunoglobulin light chain (igg3). Chain: a, c. Immunoglobulin heavy chain (igg3). Chain: b, d

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Strain: balb/c. Other_details: ascites. Other_details: ascites

Resolution:

2.60Å R-factor: 0.238 R-free: 0.291

Authors:

C.L.Brooks,R.J.Blackler,S.V.Evans

Key ref:

C.L.Brooks et al. (2010). The role of CDR H3 in antibody recognition of a synthetic analog of a lipopolysaccharide antigen. Glycobiology, 20, 138-147. PubMed id: 19767317

Date:

05-Aug-09 Release date: 06-Oct-09

Protein chains

No UniProt id for this chain

Struc: 217 a.a.

Protein chains

No UniProt id for this chain

Struc: 221 a.a.

Glycobiology 20:138-147 (2010)

PubMed id: 19767317

The role of CDR H3 in antibody recognition of a synthetic analog of a lipopolysaccharide antigen.

C.L.Brooks, R.J.Blackler, G.Sixta, P.Kosma, S.Müller-Loennies, L.Brade, T.Hirama, C.R.MacKenzie, H.Brade, S.V.Evans.

ABSTRACT

In order to explore the structural basis for adaptability in near germline monoclonal antibodies (mAb), we have examined the specificity of the promiscuous mAb S67-27 to both naturally derived carbohydrate antigens and a variety of synthetic nonnatural antigens based on the bacterial lipopolysaccharide component 3-deoxy-alpha-D-manno-oct-2-ulosonic acid (Kdo). One such analog, a 7-O-methyl (7-O-Me) Kdo disaccharide, was found to bind to the antibody with at least 30-fold higher affinity than any other antigen tested. The structure of S67-27 in complex with this analog and three other naturally occurring Kdo antigens revealed that the enhanced affinity of the mAb for the synthetic analog was accomplished by the strategic positioning of CDR H3 away from a conserved Kdo binding pocket that allowed the formation of new antibody-antigen contacts. Furthermore, the comparison of this structure with the structures of related mAbs revealed how the position and structure of CDR H3 influence the specificity or promiscuity of near-germline carbohydrate-recognizing antibodies by altering the architecture of the combining site.