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

The Linderstrom-Lang model describes proton exchange as proceeding from an 'open' state which is in equilibrium with a 'closed' state from which excha nge cannot occur. This predicts a biexponential exchange process, although limiting conditions can give rise to monoexponential exchange profiles. Whe n monoexponential exchange profiles are observed, insufficient information is present to define the exchange mechanism. We have directly observed a bi exponential exchange process, enabling us to distinguish between alternativ e amide proton exchange models. Our results are not compatible with the sta ndard local unfolding model, in which units of secondary structure open in a concerted fashion, with each of the newly exposed amide protons exchangin g at the same rate which they would in random coil peptides.