Water-inserted alpha-helical segments implicate reverse turns as folding intermediates.

Abstract

Information relevant to the folding and unfolding of alpha helices has been extracted from an analysis of protein structures. The alpha 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 alpha-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 alpha helices. Since the alpha helix, most turns, and the extended beta strand occupy contiguous regions in the conformational space of phi, psi dihedral angles, a plausible pathway can be proposed for the folding-unfolding process of alpha helices in aqueous solution.