Kinetics and thermodynamics of beta 2-microglobulin binding to the alpha 3 domain of major histocompatibility complex class I heavy chain

Biochemistry
A M HebertS Kozlowski

Abstract

The 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 beta2-microglobulin (beta2m). beta2m has been previously shown to play an important role in the folding of the MHC heavy chain without continued beta2m association with the MHC complex. Therefore, beta2m 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 beta2m is dependent on initial binding to only one of the two beta2m interfaces with class 1 heavy chain. beta2-Microglobulin binding to an isolated alpha3 domain of the class I MHC heavy chain accurately models the biochemistry and thermodynamics of beta2m-driven refolding. Our results explain a 1000-fold discrepancy between beta2m 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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Citations

Dec 26, 2002·Journal of Molecular Recognition : JMR·Rebecca L Rich, David G Myszka
Nov 26, 2002·Tissue Antigens·W T N SwelsenE M van den Berg-Loonen
Oct 21, 2004·Biological Chemistry·Cynthia Anne WrightSebastian Springer
Sep 29, 2007·Journal of Molecular Recognition : JMR·Andrei Zhukov, Robert Karlsson
Apr 1, 2013·Molecular Informatics·Christian P KochGisbert Schneider
Sep 9, 2009·International Journal of Immunogenetics·F ZhuL Yan
Dec 18, 2014·Tissue Antigens·V B G CrijnsM G J Tilanus
Mar 8, 2003·Tissue Antigens·S T CoxA-M Little
Oct 16, 2015·The Journal of Biological Chemistry·Nikolaos G SgourakisDavid H Margulies
Aug 4, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yusuke KambeTetsuji Yamaoka

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