Amyloid Fiber Formation in Human gamma D-Crystallin Induced by UV-B Photodamage

作者：Moran Sean D; Zhang Tianqi O; Decatur Sean M; Zanni Martin T^*

来源：Biochemistry, 2013, 52(36): 6169-6181.

DOI：10.1021/bi4008353

gamma D-Crystallin is an abundant structural protein of the lens that is found in native and modified forms in cataractous aggregates. We establish that UV-B irradiation of gamma D-Crystallin leads to structurally specific modifications and precipitation via two mechanisms: amorphous aggregates and amyloid fibers. UV-B radiation causes cleavage of the backbone, in large measure near the interdomain interface, where side chain oxidations are also concentrated. 2D IR spectroscopy and expressed protein ligation localize fiber formation exclusively to the C-terminal domain of gamma D-Crystallin. The native beta-sandwich domains are not retained upon precipitation by either mechanism. The similarities between the amyloid forming pathways when induced by either UV-B radiation or low pH suggest that the propensity for the C-terminal beta-sandwich domain to form amyloid beta-sheets determines the misfolding pathway independent of the mechanism of denaturation.

• 出版日期2013-9-10