Water-Inserted α-Helical Segments Implicate Reverse Turns as Folding Intermediates

Abstract

Information relevant to the folding and unfolding of α helices has been extracted from an analysis of protein structures. The α helices in protein crystal structures have been found to be hydrated, either externally by a water molecule hydrogen bonding to the backbone carbonyl oxygen atom, or internally by inserting into the helix hydrogen bond and forming a hydrogen-bonded bridge between the backbone carbonyl oxygen and the amide nitrogen atoms. The water-inserted α-helical segments display a variety of reverse-turn conformations, such as type III, type II, type I, and opened out, that can be considered as folding intermediates that are trapped in the folding-unfolding process of α helices. Since the α helix, most turns, and the extended β strand occupy contiguous regions in the conformational space of φ, ψ dihedral angles, a plausible pathway can be proposed for the folding-unfolding process of α helices in aqueous solution.