title: Amyloid fiber formation in human γD-Crystallin induced by UV-B photodamage.
abstract: γD-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 γD-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 γD-Crystallin. The native β-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 β-sandwich domain to form amyloid β-sheets determines the misfolding pathway independent of the mechanism of denaturation.
authors: Department of Chemistry, University of Wisconsin-Madison , 1101 University Avenue, Madison, WI, United States 53706.
authors: Sean D
authors: SD
authors: Moran
authors: Tianqi O
authors: TO
authors: Zhang
authors: Sean M
authors: SM
authors: Decatur
authors: Martin T
authors: MT
authors: Zanni
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D016229:Amyloid beta-Peptides / Q000737:chemistry; D002386:Cataract / Q000209:etiology; D006801:Humans; D007908:Lens, Crystalline / Q000528:radiation effects*; D046529:Microscopy, Electron, Transmission; D011489:Protein Denaturation; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D013055:Spectrophotometry, Infrared; D014466:Ultraviolet Rays; D038222:gamma-Crystallins / Q000737:chemistry / Q000528:radiation effects*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; C504903:CRYGD protein, human; D038222:gamma-Crystallins
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