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

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 N(i+1)–H∙∙∙N(i) and intraresidue N(i+1)–H∙∙∙O=C(i+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.