Mutational Analysis of 48G7 Reveals that Somatic Hypermutation Affects Both Antibody Stability and Binding Affinity

Autor:	Sophie B. Sun, Shiladitya Sen, Nam-Jung Kim, Thomas J. Magliery, Peter G. Schultz, Feng Wang
Rok vydání:	2013
Předmět:	Models Molecular Binding Sites Colloid and Surface Chemistry Protein Conformation Protein Stability DNA Mutational Analysis Mutation Temperature Antibodies Monoclonal General Chemistry Biochemistry Article Catalysis
Zdroj:	Journal of the American Chemical Society. 135:9980-9983
ISSN:	1520-5126 0002-7863
DOI:	10.1021/ja402927u
Popis:	The monoclonal antibody 48G7 differs from its germline precursor by 10 somatic mutations, a number of which appear to be functionally silent. We analyzed the effects of individual somatic mutations and combinations thereof on both antibody binding affinity and thermal stability. Individual somatic mutations that enhance binding affinity to hapten decrease the stability of the germline antibody; combining these binding mutations produced a mutant with high affinity for hapten but exceptionally low stability. Adding back each of the remaining somatic mutations restored thermal stability. These results, in conjunction with recently published studies, suggest an expanded role for somatic hypermutation in which both binding affinity and stability are optimized during clonal selection.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e38f276162ebf7316bc0ff37f9971b29 https://doi.org/10.1021/ja402927u Zobrazit plný text záznamu