Bifurcated Hydrogen Bonds and the Fold Switching of Lymphotactin.

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 2-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 β2 and β3 strands and ease the transition between the hydrogen bond pattern by which the central three-stranded β-sheet in the two forms differs.