High-resolution Crystal Structure of β2-Microglobulin Formed at pH 7.0


Kentaro Iwata, Takanori Matsuura, Kazumasa Sakurai, Atsushi Nakagawa, and Yuji Goto

Institute for Protein Research, Osaka University, and CREST, Japan Science and Technology Agency, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan

Journal of Biochemistry, 142(3), 413-419 (2007)

β2-Microglobulin (β2-m), a light chain of the major histocompatibility complex class I, forms amyloid fibrils in patients undergoing long-term hemodialysis, causing dialysis-related amyloidosis. Based on a comparison of the X-ray structure obtained at pH 5.7 and that of β2-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 β2-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 β2-m at pH 7.0 at a resolution of up to 1.13  Å. The crystal structure at pH 7.0 was basically the same as that at pH 5.6, suggesting that the conversion of the β-bulge in strand D into a contiguous β-strand is not unique to the crystals formed under slightly acidic conditions. In other words, although the formation of β2-m fibrils was enhanced under acidic conditions, it remains unknown if it is related to the increased propensity for the disappearance of the β-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.




Back toResearch Activity


MATSUURA Takanori
t.matsuu%gmail.com (Please change the mark “%” to “@”)

Valid XHTML 1.1! Valid CSS!