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 analyses of protein sequence databases, approximately 15% of the residues occur in segments of extreme compositional bias, and approximately 34% of proteins have at least one such interspersed segment. Sequences of many elongated non-globular domains also have non-random compositional bias, and these regions increase the proportion of residues in statistically deviant segments to approximately 25% of the database. In contrast, less than 1 of residues in known ordered crystal structures are in segments of reduced complexity. Increasingly, low-complexity segments have been implicated in crucial biological functions, shown by genetic engineering and mutagenesis experiments, variations in human disease and locations of autoimmune epitopes, but relatively little is known about their range of possible molecular structures, dynamics and interactions.