Kinetics and Thermodynamics of β2-Microglobulin Binding to the α3 Domain of Major Histocompatibility Complex Class I Heavy Chain
2001; American Chemical Society; Volume: 40; Issue: 17 Linguagem: Inglês
10.1021/bi002392s
ISSN1943-295X
AutoresAndrea Hebert, Jason Strohmaier, Mary C. Whitman, Trina Chen, Elena Gubina, Dawn M. Hill, Marc S. Lewis, Steven Kozlowski,
Tópico(s)Monoclonal and Polyclonal Antibodies Research
ResumoThe major histocompatibility complex (MHC) class I molecule plays a crucial role in cytotoxic lymphocyte function. Functional class I MHC exists as a heterotrimer consisting of the MHC class I heavy chain, an antigenic peptide fragment, and β2-microglobulin (β2m). β2m has been previously shown to play an important role in the folding of the MHC heavy chain without continued β2m association with the MHC complex. Therefore, β2m is both a structural component of the MHC complex and a chaperone-like molecule for MHC folding. In this study we provide data supporting a model in which the chaperone-like role of β2m is dependent on initial binding to only one of the two β2m interfaces with class 1 heavy chain. β2-Microglobulin binding to an isolated α3 domain of the class I MHC heavy chain accurately models the biochemistry and thermodynamics of β2m-driven refolding. Our results explain a 1000-fold discrepancy between β2m binding and refolding of MHC1. The biochemical study of the individual domains of complex molecules is an important strategy for understanding their dynamic structure and multiple functions.
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