On the turning away

The functional properties of a protein depend mainly on its three-dimensional (3D) structure. They are classically assigned, visualized and analysed through the prism of classical secondary structures composed of repetitive parts (α-helices for 1/3 rd of the residues and β-strands for 1/5 th , resp.) connected by coil. Two other repetitive structures also exist, namely the PolyProline II and the β-turns. The β-turns have been characterized by a hydrogen bond between N-H and C=O of residues i and i +3 by Venkatachalam [1]. He also characterized the first β-turn types. Later novel turns were defined, some being discarded, leading to a final collection of type I, I’, II, II’, IV, VIa1, VIa2, VIb, and VIII β-turns. Types VIa1, VIa2 and VIb are characterized by the presence of a cis-Proline at residue i +2. Turns that do not fit any of the above criteria are classified as type IV [2]. β-turn IV, i . e . the miscellaneous category, represents near 1/3 rd of β-turn residues in protein structure, and is the second most frequent β -turn. 25 years have passed since the last proposition of an extension of the classical definition of β-turns. Over all we have known, it seems a good moment to dig them and to see if some new recurrent conformations are not hidden into this miscellaneous type. An automatic clustering approach based on the rules of β-turn type assignment was designed to search for recurrent new turns inside this miscellaneous type. The four most occurring clusters defined the new β-turn types. Surprisingly, these types, named IV 1 , IV 2 , IV 3 and IV 4 , represent half of the type IV β-turns, and are more frequent that many established ones. Type IV 1 , is in the neighbourhood of type II but with very different amino acid composition, while IV 2 is close to type VIII with related amino acid content. Types IV 3 and IV 4 are in the same dihedral angle region than frequent β-turn type I, but with distinct dihedral angle values [3]. [1] Venkatachalam CM (1968) Stereochemical criteria for polypeptides and proteins. V. Conformation of a system of three linked peptide units. Biopolymers 6:1425-1436. [2] Hutchinson EG, Thornton JM (1996) PROMOTIF--a program to identify and analyze structural motifs in proteins. Protein Sci 5:212-220. [3] de Brevern AG (2016) Extension of the classical classification of β-turns. Sci Rep. 2016 Sep 15;6:33191.