Structural homology of lens crystallins. A method to detect protein structural homology from primary sequences.

The X-ray crystallographic structure of bovine gamma-crystallin shows four similar folding motifs each composed of about 42 residues arranged as four topologically sequential, anti-parallel beta-strands. Since the beta and gamma-crystallin sequences show good homology, proposals for a four-motif beta-crystallin model have been made. The other bovine eye-lens protein species, alpha-crystallins, are not homologous to beta or gamma-crystallin in primary structure. In the present work, smoothed plots of amino acid sequence number versus 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 four peaks separated by about 42 residues for the alpha-crystallins, suggesting that they also possess a four-motif beta-barrel structure. The physical parameter comparison technique appears generally applicable in suggesting a structural and functional relationship amongst proteins that show no primary sequence homology.