title: A comparison of structural relationships among alpha-crystallin, human Hsp27, gamma-crystallins and beta B2-crystallin.
abstract: The 3D structures of alpha-crystallin, a major eye lens protein, and related small heat shock proteins are unresolved. It has been assumed that alpha-crystallin is primarily a beta-sheet globular protein similar to alpha-crystallin (Siezen and Argos, Biochim. Biophys. Acta, 1983, 748, 56-67) containing sequence repeats in its two domains (Wistow, FEBS Lett. 1985, 181, 1-6). Positional flexibility of amino acid residues and far UV-circular dichroism spectroscopy were used to investigate structural relationships among these proteins. The utility of flexibility plots for predicting protein structure is demonstrated by the excellent correlation of these plots with the known 3D X-ray structures of beta/gamma-crystallins. Similar analyses of alpha-crystallin subunits, alpha A and alpha B, and human heat shock protein 27 show that the C-terminal domains and connecting segments of these proteins are very similar while the N-terminal domains have significant structural differences. Unlike beta/gamma-crystallins, both Hsp27 and alpha-crystallin subunits are asymmetrical with highly flexible C-terminal domains. Flexibility is considered essential for protein functional activity. Therefore, the C-terminal region may play an active role in alpha-crystallin and small heat shock protein function. Differences in flexibility profiles and estimated secondary structure distribution in alpha-crystallin by three recent/updated algorithms from far UV-CD spectra support our predicted 3D structure and the concept that alpha-crystallin and members of beta/gamma superfamily are structurally dissimilar.
authors.affiliation: Department of Ophthalmology, UMDNJ-New Jersey Medical School, Newark 07103, USA.
authors.forename: K
authors.initials: K
authors.lastname: Singh
authors.forename: D
authors.initials: D
authors.lastname: Zewge
authors.forename: B
authors.initials: B
authors.lastname: Groth-Vasselli
authors.forename: P N
authors.initials: PN
authors.lastname: Farnsworth
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003459:Crystallins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D006360:Heat-Shock Proteins / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014466:Ultraviolet Rays
chemical_list: D003459:Crystallins; D006360:Heat-Shock Proteins