Structural Homology of Lens Crystallins

Abstract

The X-ray crystallographic structure of bovine .gamma.-crystallin shows 4 similar folding motifs, each composed of .apprx. 42 residues arranged as 4 topologically sequential, anti-parallel .beta.-strands. Since the .beta. and .gamma.-crystallin sequences show good homology, proposals for a 4-motif .beta.-crystallin model were made. The other bovine eye-lens protein species, .alpha.-crystallins, are not homologous to .beta. or .gamma.-crystallin in primary structure. Smoothed plots of amino acid sequence number vs. a residue characteristic (e.g., hydrophobicity) were calculated for the various crystallins. Cross-correlation coefficients were then determined between pairs of crystallin plots for various registers of the curves. The correlation plots were then combined for several characteristics and for pairwise comparisons between .beta. or .gamma.-crystallin and the .alpha.-crystallins. The resulting plots showed 4 peaks separated by .apprx. 42 residues for the .alpha.-crystallins, suggesting that they also possess a 4-motif .beta.-barrel structure. The physical parameter comparison technique appears generally applicable in suggesting a structural and functional relationship among proteins that show no primary sequence homology.