Protein Sequence Modules

Abstract

Conserved protein sequence segments are commonly believed to correspond to functional sites in the protein sequence. A novel approach is proposed to profile the changing degree of conservation along the protein sequence, by evaluating the occurrence frequencies of all short oligopeptides of the given sequence in a large proteome database. Thus, a protein sequence conservation profile can be plotted for every protein. The profile indicates where along the sequences the potential functional (conserved) sites are located. The corresponding oligopeptides belonging to the sites are very frequent across many prokaryotic species. Analysis of a representative set of such profiles reveals a common feature of all examined proteins: they consist of sequence modules represented by the peaks of conservation. Typical size of the modules (peak-to-peak distance) is 25-30 amino acid residues.

From protein sequence space to elementary protein modules

“…Such a calculation including sequence representatives of a large variety of folds from the prokaryotic proteomes, resulted in estimates of about 10-15 amino acids for the widths of the isolated peaks for various levels of sequence identity between the fragments (data not shown). With additional 20 residues that makes the module size 30-35 residues, which is a good match to the earlier estimate of 25-30 residues for the closed loops in globular proteins (Berezovsky et al, 2000(Berezovsky et al, , 2001Aharonovsky and Trifonov, 2005).…”

“…This confinement already indicates that, perhaps, the long sequences actually consist of shorter modules. Indeed, the nearly standard size protein units of 25-30 residues have been observed in numerous studies (Benner et al, 1993;Roy et al, 1999;Sato et al, 1999;Berezovsky et al, 2000;Qian and Goldstein, 2001;Angelov et al, 2002;Voigt et al, 2002;Berezovsky et al, 2003a;Berezovsky et al, 2003b;Aharonovsky and Trifonov, 2005;Sobolevsky and Trifonov, 2006;Yew et al, 2007).…”

A Frequency-Based Linguistic Approach to Protein Decoding and Design: Simple Concepts, Diverse Applications, and the SCS Package

“…A related study proposed “protein conservation profile” [45]. This is a simple frequency plot along a given amino acid sequence and thus different from our availability plot, which shows availability scores of SCSs along a given amino acid sequence.…”

Primordia Vita. Deconvolution from Modern Sequences.

“…The hypothetical small molecule could have been ancestral to the ABC transporters, or one of the modules of which the transporters are built. The modular structure of modern proteins is suggested by sequence conservation plots where the numerous highly conserved short motifs are indicated by sharp peaks at various sequence positions (Aharonovsky and Trifonov 2005).…”