Structural and functional analyses of PolyProline-II helices in globular proteins.

Abstract

PolyProline-II (PPII) helices are defined as a continuous stretch of a protein chain in which the constituent residues have backbone torsion angle (φ, ψ) values of (-75°, 145°) and take up an extended left handed helical conformation, without any intra-chain hydrogen bonds. They are found to occur quite frequently in protein structures, with their number exceeding that of π-helices, though it is considerably less than that of α-helices and β-strands. A relatively new procedure, ASSP, for the identification of regular secondary structures using Cα trace identifies 3597 PPII-helices in 3582 protein chains, solved at resolution ⩽2.0Å. Taking advantage of this significantly expanded database of PPII-helices, we have analyzed their structural and functional roles as well as determined the amino acid propensity within and around them. Though Pro residues are highly preferred, their presence is not a mandatory requirement for the formation of PPII-helices, since ∼40% PPII-helices were found to contain no Pro residues. Aromatic amino acids are avoided within this helix, while Gly, Asn and Asp residues are preferred in the proximal flanking regions. The PPII-helices range from 3 to 13 residues in length with the average twist and rise being -121.2°±9.2° and 3.0ű0.1Å respectively. A majority (∼72%) of PPII-helices were found to occur in conjunction with α-helices and β-strands, and serve as linkers as well. The analysis of various intra-helical non-bonded interactions revealed frequent presence of CH⋯O H-bonds. PPII-helices participate in maintaining the three-dimensional structure of proteins and are important constituents of binding motifs involved in various biological functions.