title: High-resolution crystal structure of beta2-microglobulin formed at pH 7.0.
abstract: beta(2)-Microglobulin (beta2-m), a light chain of the major histocompatibility complex class I, forms amyloid fibrils in patients undergoing long-term haemodialysis, causing dialysis-related amyloidosis. Based on a comparison of the X-ray structure obtained at pH 5.7 and that of beta2-m in the histocompatibility complex, it has been proposed that the continuous D-strand observed in the crystal structure at pH 5.7 increases the propensity of beta2-m to self-associate via edge-to-edge interactions, thus initiating the formation of fibrils. To obtain further insight into the mechanism by which amyloid fibrils form, we determined the crystal structure of beta2-m at pH 7.0 at a resolution of up to 1.13 A. The crystal structure at pH 7.0 was basically the same as that at pH 5.6, suggesting that the conversion of the beta-bulge in strand D into a contiguous beta-strand is not unique to the crystals formed under slightly acidic conditions. In other words, although the formation of beta2-m fibrils was enhanced under acidic conditions, it remains unknown if it is related to the increased propensity for the disappearance of the beta-bulge in strand D. We consider that the enhanced fibrillation is more directly coupled with the decreased stability leading to the increased propensity of exposing amyloidogenic regions.
authors.affiliation: Institute for Protein Research, Osaka University, and CREST, Japan Science and Technology Agency, Yamadaoka 3-2, Suita, Osaka, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Iwata
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsuura
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Sakurai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakagawa
authors.forename: Yuji
authors.initials: Y
authors.lastname: Goto
mesh_terms: D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D001613:beta 2-Microglobulin / Q000737:chemistry*
chemical_list: D001613:beta 2-Microglobulin