A COMPARISON OF STRUCTURAL RELATIONSHIPS AMONG ALPHA-CRYSTALLIN, HUMAN HSP27, GAMMA-CRYSTALLINS AND BETA-B2-CRYSTALLIN

The 3D structures of alpha-crystallin, a major eye lens protein, and r elated small heat shock proteins are unresolved. It has been assumed t hat alpha-crystallin is primarily a beta-sheet globular protein simila r to gamma-crystallin (Siezen and Argos, Biochim. Biophys. Acta, 1983, 748, 56-67) containing sequence repeats in its two domains (Wistow, F EES Lett. 1985, 181, 1-6). Positional flexibility of amino acid residu es and far UV-circular dichroism spectroscopy were used to investigate structural relationships among these proteins. The utility of flexibi lity plots for predicting protein structure is demonstrated by the exc ellent correlation of these plots with the known 3D X-ray structures o f beta/gamma-crystallins. Similar analyses of alpha-crystallin subunit s, 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 diffe rences. Unlike beta/gamma-crystallins, both Hsp27 and alpha-crystallin subunits are asymmetrical with highly flexible C-terminal domains. Fl exibility is considered essential for protein functional activity. The refore, the C-terminal region may play an active role in alpha-crystal lin and small heat shock protein function. Differences in flexibility profiles and estimated secondary structure distribution in alpha-cryst allin by three recent/updated algorithms from far UV-CD spectra suppor t our predicted 3D structure and the concept that alpha-crystallin and members of beta/gamma superfamily are structurally dissimilar. Copyri ght (C) 1996 Elsevier Science B.V.