Comparison of ARM and HEAT protein repeats

ARM and HEAT motifs are tandemly repeated sequences of approximately 50 ami no acid residues that occur in a wide variety of eukaryotic proteins. An ex haustive search of sequence databases detected new family members and revea led that at least 1 in 500 eukaryotic protein sequences contain such repeat s. It also rendered the similarity between ARM and HEAT repeats, believed t o be evolutionarily related, readily apparent. All the proteins identified in the database searches could be clustered by sequence similarity into fou r groups: canonical ARM-repeat proteins and three groups of the more diverg ent HEAT-repeat proteins. This allowed us to build improved sequence profil es for the automatic detection of repeat motifs. Inspection of these profil es indicated that the individual repeat motifs of all four classes share a common set of seven highly conserved hydrophobic residues, which in protein s of known three-dimensional structure are buried within or between repeats . However, the motifs differ at several specific residue positions, suggest ing important structural or functional differences among the classes. Our r esults illustrate that ARM and HEAT-repeat proteins, while having a common phylogenetic origin, have since diverged significantly. We discuss evolutio nary scenarios that could account for the great diversity of repeats observ ed. (C) 2001 Academic Press.