title: Transglutaminase-mediated cross-linking of alpha-crystallin: structural and functional consequences.
abstract: Aggregation and covalent cross-linking of the crystallins, the major structural proteins of the eye lens, increase light scattering by the lens leading to opacification and cataract. Disturbance of calcium homeostasis in the tissue is one of the factors implicated in cataractogenesis. Calcium-activated transglutaminase (TG)-catalyzed cross-linking of some lens proteins has been reported earlier. We show here that alpha-crystallin, a major structural protein in the lens and a member of the small heat shock protein family, is also a substrate for TG-mediated cross-linking, indicating the presence of donor Lys and acceptor Gln residues in the protein. Upon TG-catalyzed dimerization, the secondary and tertiary structures of the protein are altered, and its surface hydrophobicity reduced. The chaperone-like property of the protein, suspected to be one of its functions in situ, is substantially reduced upon such cross-linking. These results, taken together with earlier ones on lens beta-crystallins and vimentin, suggest that TG-mediated events might compromise lens function. Also, since alpha-crystallin occurs not only in the lens but in other tissues as well, such TG-catalyzed cross-linking and the associated alterations in its structure and activity would be of general pathological interest.
authors: Centre for Cellular and Molecular Biology, Hyderabad, India.
authors: P
authors: P
authors: Shridas
authors: Y
authors: Y
authors: Sharma
authors: D
authors: D
authors: Balasubramanian
mesh_terms: D000818:Animals; D002417:Cattle; D003459:Crystallins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D019281:Dimerization; D006168:Guinea Pigs; D006801:Humans; D007908:Lens, Crystalline / Q000201:enzymology*; D018832:Molecular Chaperones / Q000737:chemistry; D011487:Protein Conformation; D011503:Transglutaminases / Q000378:metabolism*
chemical_list: D003459:Crystallins; D018832:Molecular Chaperones; D011503:Transglutaminases