SEQUENCES WITH UNUSUAL AMINO-ACID COMPOSITIONS

Amino acid sequences of very non-random composition ('low-complexity' segments) are abundant in natural proteins. From recent statistical an alyses of protein sequence databases, approximately 15% of the residue s occur in segments of extreme compositional bias, and approximately 3 4% of proteins have at least one such interspersed segment. Sequences of many elongated non-globular domains also have non-random compositio nal bias, and these regions increase the proportion of residues in sta tistically deviant segments to approximately 25% of the database. In c ontrast, less than 1% of residues in known ordered crystal structures are in segments of reduced complexity. Increasingly, low-complexity se gments have been implicated in crucial biological functions, shown by genetic engineering and mutagenesis experiments, variations in human d isease and locations of autoimmune epitopes, but relatively little is known about their range of possible molecular structures, dynamics and interactions.