Bifurcated Hydrogen Bonds and the Fold Switching of Lymphotactin

Abstract

Lymphotactin (Ltn) exists under physiological conditions in an equilibrium between two interconverting structures with distinct biological functions. Using Replica-Exchange-with-Tunneling we study the conversion between the two folds. Unlike previously proposed, we find that the fold switching does not require unfolding of Lymphotactin, but proceeds through a series of intermediates that remain partially structured. This process relies on two bifurcated hydrogen bonds that connect the {beta}2 and {beta}3 strands and eases the transition between the hydrogen bond pattern by which the central three-stranded {beta}-sheet in the two forms differ.