[Unique Combinations of ßαß-Units and Π-Like Modules in Proteins and Specific Features of Their Amino Acid Sequences].

Possible combinations of ßαß-units and Π-like modules in proteins in both right- and left-handed forms have been analyzed in detail. The correlation between the mutual arrangement of the structural elements in the polypeptide chain and their handedness has been shown. In the ßαßП combinations, which is encountered most frequently in proteins, the П-module follows the ßαß unit along the chain and both elements are right-handed. In the Пßαß combinations, where the П-module is located at the N end and the ßαß-unit follows it, the former is left-handed and the latter is right-handed. In relatively rare combinations of the left-handed ßαß-units and right-handed П-modules, the ßαß-unit follows П-module in the chain. The combinations of left-handed П-modules and the left-handed ßαß-units are unobservable in proteins. It has also been shown that the П-modules with a ß-strand-α-helix-arch-ß-strand structure are observed in proteins only in a right-handed form and half of them (51%) contains cis-prolines in their arches. These arches of nonhomologous proteins, as well as the positions of cis-prolines, nearly coincide when superimposed. The superimposed П-modules also demonstrate that their overall folds are very similar. Structural alignment of their amino acid sequences has shown that the П-modules have very similar sequence patterns of the key hydrophobic, hydrophilic, glycine, and cis-proline residues.

[Structure and Features of Amino Acid Sequences of L-Modules in SH3-Like Folds].

A novel L-shaped repeat module whose structure can be represented as ß-strand-loop-ß-strand has been identified in a stereochemical analysis of nonhomologous SH3-like folds. ß-Strands of the L-module are positioned at a ~90° angle to each other in different orthogonally packed ß-layers. Together with a crossover loop, they form a half-turn of a right-handed superhelix. A database of 60 nonhomologous SH3-like domains has been compiled using the Protein Data Bank to study structural similarities and differences of L-modules. Occurrence frequencies of L-modules have been determined depending on the length of their loops. It has been shown that L-modules with ßmαααßn- and ßmαααßαßn-conformations, where m and n are numbers of ß-residues in the first and second ß-strands, occur most often (57 and 8%, respectively). Spatial structures of L-modules of the same type are very similar, demonstrated through superimposing them using computer programs. Structural alignment of the amino acid sequences encoding L-modules has been performed, making it possible to identify key positions for hydrophobic, hydrophilic, and proline residues.

A novel structural motif and structural trees for proteins containing it.

In the present study, a novel structural motif that can be represented as a combination of the known betaalphabeta-unit and psi-motif is described and analyzed. In theory, there are four possible combinations of the motifs since each of them can exist in two forms, left-handed and right-handed. For this study, we have selected 140 nonhomologous proteins in which 158 combinations of such types have been found. The combination of the right-handed psi-motif and the right-handed betaalphabeta-unit has been shown to occur most often (87 cases out of 158) and the combination of the left-handed betaalphabeta-unit and the left-handed psi-motif does not occur at all. Three novel structural trees in which the commonly occurring combinations are taken as the root structures have been constructed.

[Side-chain rotamers in protein alpha-alpha-hairpins and a mechanism of their selection].

The observed features of side-chain rotamer distributions in protein alpha-alpha-hairpins are described. It was found that in left-turned alpha-alpha-hairpins most side chains occupying d-positions have t-rotamers and those in g-positions g- -rotamers. In right-turned alpha-alpha-hairpins, most side chains in a-positions adopt g- -rotamers and those in e-positions t-rotamers. Analysis of these features enables us to conclude that selection of side-chain rotamers in alpha-alpha-hairpins depends on both the type of the alpha-helix packing and the residue position. The observed features can be explained taking into account the squeezing mechanism according to which interhelical interactions bring alpha-helices closer to each other and this effect squeezes side chains out of the helix-helix interface and as a result they adopt unique conformations.