Random Coils of Proteins Situated Between a Beta Strand and an Alpha Helix Demonstrate Decreased Solvent Accessibility.

Abstract

Surface accessibility of different types of the same elements of secondary structure has been studied in 10 non-redundant sets of proteins (total number of three-dimensional structures is 1730) with a help of DSSP (Dictionary of Secondary Structure of Proteins). Random coils (C), beta strands (B), and alpha helices (H) have been classified according to their flanking elements of secondary structure in a polypeptide chain. Thanks to this kind of classification, for the first time it has been shown that random coils situated between a beta strand and an alpha helix (BCH) contain significantly lower fraction of exposed residues compared to other types of random coils; the least accessible beta strands are situated between two alpha helices (HBH), and the least accessible alpha helices are situated between a beta strand and an alpha helix (BHH). Discovered trends are explained as consequences of the natural selection that had been stabilizing the secondary structure of proteins on early steps of their evolution. Acquired differences in amino acid content of different types of random coils, alpha helices, and beta strands led to the formation of partially buried but hydrophilic BCH random coils because of their enrichment by Ser, Thr, and Asp residues. As a result, BCH random coils became prone to bind cations because of their lower hydration and decreased usage of positively charged amino acid residues. The mechanism described above led to the formation of active centers in ancient metalloenzymes. Nowadays one can observe decreased surface accessibility of amino acid residues in BCH random coils, in HBH beta strands, and in BHH alpha helices in proteins possessing hydrophobic cores.