On the pathway of the formation of secondary structures in proteins

Protein structures are typically made up of well-defined modules, called secondary structures. A hierarchical model of protein folding may start with the formation of five-membered non-covalently-linked ring motifs involving O & sdot;& sdot;& sdot;C=O and N-H<middle dot><middle dot><middle dot>N interactions connecting two consecutive peptide groups. Some of these interactions lead to polyproline II structure, which are known to occur in the unfolded state of proteins. These interactions constitute different types of gamma-turns, providing the sharpest reversal of the chain direction. Occurring transiently in the unfolded state, and in tandem, they can lead to beta-turns. One of the beta-turns (type I) is predisposed (from a consideration of residue usage) to form the N-terminal of an alpha-helix, which then propagates toward its C-terminal direction. O & sdot;& sdot;& sdot;C=O interactions encompass four distinct types of conformational features, and one of them has very similar backbone torsion angles as the polyproline II (PPII) conformation and can thus contribute to the formation of PPII helix. An adjustment from these angles can also drive the formation of beta-strand. N-H<middle dot><middle dot><middle dot>N interactions can also constitute capping interaction at helix termini and can link a PPII helix to an alpha-helix. Thus, the polypeptide backbone is endowed with all the features that can initiate the formation of secondary structural elements, and the gamma-turn motifs (resulting from O & sdot;& sdot;& sdot;C=O and N-H<middle dot><middle dot><middle dot>N interactions) are the basic units the protein structures are made up of.