Correlation of observed fold frequency with the occurrence of local structural motifs

It is well known that some protein folds (superfolds) occur very frequently. We show that compared to other folds, most superfold structures have a higher proportion of their alpha-helical or beta-strand residues in one of three basic units of supersecondary structure (alpha-hairpin, beta-hairpin or beta alpha beta-unit) Furthermore, by taking into consideration two more complex motifs, the four-stranded Greek-key (beta(4)) and the beta alpha-Greek key (beta alpha beta beta), we demonstrate that the remaining superfold structures contain many of these higher order units of three-dimensional packing. The implications of these results for folding are discussed. (C) 1999 Academic Press.