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Role of the constant region domain in the structural diversity of human antibody light chains
Author(s) -
Hifumi Emi,
Taguchi Hiroaki,
Kato Ryuichi,
Uda Taizo
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600819r
Subject(s) - chemistry , dimer , immunoglobulin light chain , divalent , molecule , cls upper limits , ion , copper , biophysics , equilibrium constant , binding site , crystallography , antibody , inorganic chemistry , biochemistry , biology , organic chemistry , medicine , optometry , immunology
Issues regarding the structural diversity (heterogeneity) of an antibody molecule have been the subject of discussion along with the development of antibody drugs. Research on heterogeneity has been extensive in recent years, but no clear solution has been reached. Heterogeneity is also observed in catalytic antibody k light chains (CLs). In this study, we investigated how the constant region domain of CLs concerns structural diversity because it is a simple and good example for elucidating heterogeneity. By means of cation‐exchange chromatography, SDS‐PAGE, and 2‐dimensional electrophoresis for the CL, multimolecular forms consisting of different electrical charges and molecular sizes coexisted in the solution, resulting in the similar heterogeneity of the full length of CLs. The addition of copper ion could cause the multimolecular forms to change to monomolecular forms. Copper ion contributed greatly to the enrichment of the dimer form of CL and the homogenization of the differently charged CLs. Two molecules of the CL protein bound one copper ion. The binding affinity of the ion was 48.0 μM 2 1 . Several divalent metal ions were examined, but only zinc showed a similar effect. —Hifumi, E., Taguchi, H., Kato, R., Uda, T. Role of the constant region domain in the structural diversity of human antibody light chains. FASEB J . 31, 1668–1677 (2017) www.fasebj.org