title: Binding of γ-crystallin substrate prevents the binding of copper and zinc ions to the molecular chaperone α-crystallin.
abstract: α-Crystallin is a small heat shock protein and molecular chaperone. Binding of Cu2+ and Zn2+ ions to α-crystallin leads to enhanced chaperone function. Sequestration of Cu2+ by α-crystallin prevents metal-ion mediated oxidation. Here we show that binding of human γD-crystallin (HGD, a natural substrate) to human αA-crystallin (HAA) is inversely related to the binding of Cu2+/Zn2+ ions: The higher the amount of bound HGD, the lower the amount of bound metal ions. Thus, in the aging lens, depletion of free HAA will not only lower chaperone capacity but also lower Cu2+ sequestration, thereby promoting oxidation and cataract.
authors.affiliation: Department of Chemistry, Life Sciences Research Building, University at Albany, State University of New York , Albany, New York 12222, United States.
authors.forename: Kalyan S
authors.initials: KS
authors.lastname: Ghosh
authors.forename: Ajay
authors.initials: A
authors.lastname: Pande
authors.forename: Jayanti
authors.initials: J
authors.lastname: Pande
mesh_terms: D000818:Animals; D002386:Cataract / Q000378:metabolism; D002417:Cattle; D003300:Copper / Q000737:chemistry*; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D011485:Protein Binding; D015032:Zinc / Q000737:chemistry*; D038202:alpha-Crystallin A Chain / Q000737:chemistry; D038201:alpha-Crystallins / Q000378:metabolism*; D038222:gamma-Crystallins / Q000378:metabolism*
chemical_list: C504903:CRYGD protein, human; D018832:Molecular Chaperones; D038202:alpha-Crystallin A Chain; D038201:alpha-Crystallins; D038222:gamma-Crystallins; D003300:Copper; D015032:Zinc