A novel secondary structure based on fused five-membered rings motif

Abstract

An analysis of protein structures indicates the existence of a novel, fused five-membered rings motif, comprising of two residues (i and i + 1), stabilized by interresidue Ni+1–H∙∙∙Ni and intraresidue Ni+1–H∙∙∙O=Ci+1 hydrogen bonds. Fused-rings geometry is the common thread running through many commonly occurring motifs, such as β-turn, β-bulge, Asx-turn, Ser/Thr-turn, Schellman motif, and points to its structural robustness. A location close to the beginning of a β-strand is rather common for the motif. Devoid of side chain, Gly seems to be a key player in this motif, occurring at i, for which the backbone torsion angles cluster at ~(−90°, −10°) and (70°, 20°). The fused-rings structures, distant from each other in sequence, can hydrogen bond with each other, and the two segments aligned to each other in a parallel fashion, give rise to a novel secondary structure, topi, which is quite common in proteins, distinct from two major secondary structures, α-helix and β-sheet. Majority of the peptide segments making topi are identified as aggregation-prone and the residues tend to be conserved among homologous proteins.

O‧‧‧C═O interaction, its occurrence and implications for protein structure and folding

“…Negative z value represents underrepresentation, whereas positive z value indicates overrepresentation. To compare with some published literature, we also had to calculate an equivalent parameter, the propensity of a residue to occur at any position as the ratio of the percentage of occurrence of that particular residue at the position to its percentage in the whole database 7 …”

“…This shows how the values of the torsion angles can be balanced so as to maintain a nearly perpendicular position of the O atoms relative to the carbonyl plane, as has also been reported at position i for the N H i+1 ‧‧‧N(p z ) i hydrogen bond. 7…”

“…Our analysis of N H i+1 ‧‧‧N(p z ) i hydrogen bond, on the other hand, has focused on regions beyond the regular secondary structure and shown how this can be part of a novel type of γ-turn, or be involved in helix capping interaction. 7,8 Following the observation of O iÀ1 ‧‧‧C i interactions in an oligoproline structure, 11 we look at the occurrence of such two-residue interaction (Figure 1A) in the nonhelical and non-sheet regions in protein structures and investigate the types of residues involved, their secondary structure, and the structural motifs that this gives rise to. We surmise that O‧‧‧C═O and N H‧‧‧N interactions generate the smallest motifs in protein structures, which are used to build up larger secondary structures, thus providing a hierarchical model of protein folding.…”

“…Numerous noncovalent interactions play essential roles in the protein structure and its function 1–6 . A few recently characterized structural motifs involve two adjacent peptide groups, such that NH group of the second interacts with the lone pair orbital on the N atom of the first, forming NH i +1 ‧‧‧N(p z ) i hydrogen bond 7–10 . Questions may be asked if what is seen at the amino end of a peptide group can also be replicated at the carbonyl end, if two such groups in the adjacent peptide planes can interact between themselves.…”

“…[1][2][3][4][5][6] A few recently characterized structural motifs involve two adjacent peptide groups, such that N H group of the second interacts with the lone pair orbital on the N atom of the first, forming N H i+1 ‧‧‧N(p z ) i hydrogen bond. [7][8][9][10] Questions may be asked if what is seen at the amino end of a peptide group can also be replicated at the carbonyl end, if two such groups in the adjacent peptide planes can interact between themselves. Indeed, the crystal structure of an oligoproline was found to exhibit polyproline II helix conformation stabilized only by O iÀ1 ÁÁÁC i interactions taking place between the carbonyl oxygens and the carbonyl carbons of neighboring residues.…”