On the presence of short-range periodicities in protein structures that are not related to established secondary structure elements.

Standard secondary structure elements such as α-helices or β-sheets, are characterized by repeating backbone torsion angles (φ,ψ) at the single residue level. Two-residue motifs of the type (φ,ψ) are also observed in nonlinear conformations, mainly turns. Taking these observations a step further, it can be argued that there is no a priori reason why the presence of higher order periodicities can not be envisioned in protein structures, such as, for example, periodic transitions between successive residues of the type (…-α-β-α-β-α-…), or (…-β-α -β-α -β-…), or (…-α-β-α -α-β-α -…), and so forth, where the symbols (α,β,α ) refer to the established Ramachandran-based residue conformations. From all such possible higher order periodicities, here we examine the deposited (with the PDB) protein structures for the presence of short-range periodical conformations comprising five consecutive residues alternating between two (and only two) distinct Ramachandran regions, for example, conformations of the type (α-β-α-β-α) or (β-α -β-α -β), and so forth. Using a probabilistic approach, we have located several thousands of such peptapeptides, and these were clustered and analyzed in terms of their structural characteristics, their sequences, and their putative functional correlations using a gene ontology-based approach. We show that such nonstandard short-range periodicities are present in a large and functionally diverse sample of proteins, and can be grouped into two structurally conserved major types. Examination of the structural context in which these peptapeptides are observed gave no conclusive evidence for the presence of a persistent structural or functional role of these higher order periodic conformations.