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Systematic classification of CDR‐L3 in antibodies: Implications of the light chain subtypes and the V L –V H interface
Author(s) -
Kuroda Daisuke,
Shirai Hiroki,
Kobori Masato,
Nakamura Haruki
Publication year - 2009
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.22230
Subject(s) - complementarity determining region , antibody , computational biology , peptide sequence , amino acid , immunoglobulin light chain , biology , chemistry , genetics , gene
Antibody modeling is widely used for the analysis of antibody–antigen interactions and for the design of potent antibody drugs. The antibody combining site is composed of six complementarity determining regions (CDRs). The CDRs, except for CDR‐H3, which is the most diverse CDR, form limited numbers of canonical structures, which can be identified from the amino acid sequences. A method to classify the CDR‐H3 structure from its amino acid sequence was previously proposed. However, since those CDR structures were classified, many more antibody crystal structures have been determined. We performed systematic analyses of the CDR‐L3 structures and found novel canonical structures, and we also classified a previously identified canonical structure into two subtypes. In addition, two differently defined canonical structures in the κ and λ subtypes were classified into the same canonical structure. We also identified a key residue in CDR‐L3, which determines the conformation of CDR‐H3. Several analyses of CDR‐L3 loops longer than nine residues were performed. These new findings should be useful for structural modeling and are eventually expected to accelerate the design of antibody drugs. Proteins 2009. © 2008 Wiley‐Liss, Inc.