NMR relaxation measurements of backbone proton exchange in proteins permit a distinction between different mechanisms of exchange

Abstract

The Linderstrøm-Lang model describes proton exchange as proceeding from an ‘open’ state which is in equilibrium with a ‘closed’ state from which exchange cannot occur. This predicts a biexponential exchange process, although limiting conditions can give rise to monoexponential exchange profiles. When monoexponential exchange profiles are observed, insufficient information is present to define the exchange mechanism. We have directly observed a biexponential exchange process, enabling us to distinguish between alternative amide proton exchange models. Our results are not compatible with the standard local unfolding model, in which units of secondary structure open in a concerted fashion, with each of the newly exposed amide protons exchanging at the same rate which they would in random coil peptides.