PDBsum entry 4bh8

Immune system

PDB id: 4bh8

Contents

Protein chains

214 a.a.

218 a.a.

Ligands

ARG-PRO-SER-TYR-ILE-SER-HIS-LEU-LEU

Waters ×190

PDB id:

4bh8

Name:

Immune system

Title:

Crystal structure of germline antibody 36-65 in complex with peptide gdprpsyishll

Structure:

Anti-ars murine germline monoclonal antibody 36-65. Chain: a. Fragment: antigen binding fragment. Anti-ars murine germline monoclonal antibody 36-65. Chain: b. Fragment: antigen binding fragment. Dodecapeptide antigen. Chain: p. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Strain: balb/c. Cell_line: 36-65 hybridoma. Organ: spleen. Cell: b cell. Synthetic: yes. Synthetic construct.

Resolution:

2.40Å R-factor: 0.231 R-free: 0.251

Authors:

T.Khan,D.M.Salunke

Key ref:

T.Khan and D.M.Salunke (2014). Adjustable locks and flexible keys: plasticity of epitope-paratope interactions in germline antibodies. J Immunol, 192, 5398-5405. PubMed id: 24790145 DOI: 10.4049/jimmunol.1302143

Date:

30-Mar-13 Release date: 16-Apr-14

Protein chain

No UniProt id for this chain

Struc: 214 a.a.

Protein chain

No UniProt id for this chain

Struc: 218 a.a.

DOI no: 10.4049/jimmunol.1302143

J Immunol 192:5398-5405 (2014)

PubMed id: 24790145

Adjustable locks and flexible keys: plasticity of epitope-paratope interactions in germline antibodies.

T.Khan, D.M.Salunke.

ABSTRACT

Ag recognition by independent primary Abs against a small flexible Ag with overlapping epitopes was analyzed to address the determinants of Ag specificity during the initial encounter. Crystal structures of two distinct dodecapeptide Ags, GDPRPSYISHLL and PPYPAWHAPGNI, in complex with the germline mAb 36-65 were determined and compared with the structures of the same Ags bound to another independent germline mAb, BBE6.12H3. For each peptide Ag, the two germline mAbs recognized overlapping epitopes, but in different topologies. The peptide structures differed, and the two paratopes attained discrete conformations, leading to different surface topologies, in a mode that can be described as adjustable locks and flexible keys. This is in contrast to mature mAbs, in which conformational convergence of different paratopes while binding to a common epitope in a similar conformation has been reported. These results suggest that the primary immune receptor repertoire is highly versatile as compared with its mature counterpart. Germline and mature mAbs adopt distinct mechanisms for recognizing a flexible epitope. Whereas conservation of conformational repertoire is a key characteristic of mature mAbs achieved through affinity maturation, the germline mAbs, at the initial stages of Ag encounter, maintain substantial plasticity, accommodating a broad specificity repertoire.