2A6K

Crystal Structure Analysis of the germline antibody 36-65 Fab in complex with the dodecapeptide SLGDNLTNHNLR

Summary for 2A6K

• Entry DOI: 10.2210/pdb2a6k/pdb
• Related: 2A6D 2A6I 2A6J
• Descriptor: Germline antibody 36-65 Fab light chain, Germline antibody 36-65 Fab heavy chain, DODECAPEPTIDE: SLGDNLTNHNLR, ... (4 entities in total)
• Functional Keywords: immunoglobulin fold, fab-peptide complex, immune system
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 5
• Total formula weight: 96655.09

Authors

Sethi, D.K.,Agarwal, A.,Manivel, V.,Rao, K.V.,Salunke, D.M. (deposition date: 2005-07-03, release date: 2006-06-13, Last modification date: 2018-03-21)

Primary citation

Sethi, D.K.,Agarwal, A.,Manivel, V.,Rao, K.V.,Salunke, D.M.
Differential epitope positioning within the germline antibody paratope enhances promiscuity in the primary immune response.
Immunity, 24:429-438, 2006

PubMed Abstract: Correlation between the promiscuity of the primary antibody response and conformational flexibility in a germline antibody was addressed by using germline antibody 36-65. Crystallographic analyses of the 36-65 Fab with three independent dodecapeptides provided mechanistic insights into the generation of antibody diversity. While four antigen-free Fab molecules provided a quantitative description of the conformational repertoire of the antibody CDRs, three Fab molecules bound to structurally diverse peptide epitopes exhibited a common paratope conformation. Each peptide revealed spatially different footprints within the antigen-combining site. However, a conformation-specific lock involving two shared residues, which were also associated with hapten binding, was discernible. Unlike the hapten, the peptides interacted with residues that undergo somatic mutations, suggesting a possible mechanism for excluding "nonspecific" antigens during affinity maturation. The observed multiple binding modes of diverse epitopes within a common paratope conformation of a germline antibody reveal a simple, yet elegant, mechanism for expanding the primary antibody repertoire.

PubMed: 16618601
DOI: 10.1016/j.immuni.2006.02.010

Experimental method

X-RAY DIFFRACTION (3 Å)