The three-dimensional structure of 2 microglobulin: Results from X-ray crystallography

beta(2)-microglobulin, the light chain component of the major histocompatibility complex 1, is involved in the development of DRA, an amyloid deposition disease occurring in man. Specifically, the beta 2-microglobulin component, dissociated form the complex heavy chain, gives rise to amyloidogenic deposits in the joints of patients exposed to long dialysis periods. beta(2)-microglobulin three-dimensional structure is based on an antiparallel beta-barrel fold, with immunoglobulin domain topology, displaying structural flexibility in the crystal and NMR structures so fare determined. The structural bases of amyloidogenic potential in beta 2-microglobulin can be related to local unfolding, to the tendency to aggregate laterally through non-compensated beta-strands, and partly also to its trend towards N-terminal proteolytic degradation. Such trends emerge quite clearly from inspection of a limited number of crystal structures of beta 2-microglobulin as an isolated chain, separated form the major histocompatibility complex I heavy chain. (c) 2005 Elsevier B.V. All rights reserved.