Convergent evolution in structural elements of proteins investigated using cross profile analysis

This report describes the development and use of "Cross Profile Analysis" to compare sequence-based profiles and structure-based profiles based on amino acid occurrences at each position within a protein segment cluster. Using systematic cross profile analysis, we found structural clusters of 9-residue and 15-residue segments showing remarkably strong correlation with particular sequence profiles. These correlations reflect structural similarities among constituent segments of both sequence-based and structure-based profiles. We also report previously undetectable sequence-structure patterns that transcend protein family and fold boundaries, and present results of the conformational analysis of the deduced peptide of a segment cluster. These results suggest the existence of ancient short-peptide ancestors.Cross profile analysis reveals the polyphyletic and convergent evolution of β-hairpin-like structures, which were verified both experimentally and computationally. The results presented here give us new insights into the evolution of short protein segments.Abundant examples of similar segments appearing in different protein folds, here continuous structural fragments in native protein folds, have been reported. Although some of those segments are believed to have originated from common ancestors, evolutionary scenarios for many of those segments are not clear. As opposed to the monophyletic scenario of presently existing protein domains, Lupas et al. argued the hypothesis of ancient short peptide ancestors [1]. They found local sequence and structure similarities such as P-loops, zinc finger motifs, and Asp boxes, in different protein folds based on results of all-against-all structural comparisons of segments using their rigorous structure comparison method. The reason they employed their structure comparison method is that occurrences of such segments 'might not be expected to be meaningful from a sequence-only perspective [1]'.Originally, the profile method was