Patterns of Sequence Variation in Families of Homologous Proteins

Summary

X-ray structure analyses of proteins and computational approaches to the comparison of three-dimensional structures provide a basis for understanding the nature of restraints on the diversity of sequences in families of homologous proteins. Detailed examples are provided by structures defined by X-ray analysis at Birkbeck for two families of homologous proteins, the beta/gamma crystallins (five proteins) and aspartic proteinases (five enzymes). In addition all families of proteins, for which two or more well-refined high-resolution structures are available in the Brookhaven Databank, have been compared. Residue to residue substitution tables have been calculated for amino acids classified according to residue type, secondary structure, accessibility of the sidechain, and existence of hydrogen bonds from sidechain to other sidechains or peptide carbonyl or amide functions. Distinct patterns of substitution characterize most classes especially where amino acid residues are both solvent inaccessible and hydrogen-bonded through their sidechains.