Structure function relationship among alpha-crystallin related small heat shock proteins

A sequence alignment is presented which permits the detection of the sequence and structural homology among alpha-crystallin subunits, alphaA and alphaB, and distantly related sHsps, MjHsp16.5 and wheat Hsp16.9. This alignment shows that homology extends beyond the alpha-crystallin domain. Variations in the polydisperse quaternary structure appear, in part, dependent upon the N-terminal 18 and 19 amino acids that are essential for subunit interactions in polydisperse sHsps. The hydrophobic sequence that follows these N-terminal amino acids shares a number of aromatic amino acids and has significant homology with MjHsp16.5. In the second exon of alpha-crystallin, sequence homology is concentrated in a region with chaperone and ANS binding sites. It is clear that the binding site for ANS and its derivative, bis-ANS, requires both positively charged amino acids and hydrophobic interactions. Therefore, its binding is not a true measure of hydrophobic surface exposure. The limited homology and secondary structure in the following C-terminal sequences is related to the pattern of association of other sHsp subunits and/or functional differences. Our study suggests that alphaA has evolved in the lens to chaperone exposed beta-sheet edges of the betagamma crystallins and their proteolytic fragments. Also, both time and a harsh environment such as that in the lens interior, beta-sheet proteins would naturally generate beta-sheet edges. The interaction between such edges results in insoluble, abnormal protein aggregation and in the lens, light scattering elements that cause cataract.