Equilibrium Unfolding Thermodynamics of β2-Microglobulin Analyzed through Native-State H/D Exchange

The exchange rates for the amide hydrogens of β2-microglobulin, the protein responsible for dialysis-related amyloidosis, were measured under native conditions at different temperatures ranging from 301 to 315 K. The pattern of protection factors within different regions of the protein correlates well with the hydrogen-bonding pattern of the deposited structures. Analysis of the exchange rates indicates the presence of mixed EX1- and EX2-limit mechanisms. The measured parameters are consistent with a two-process model in which two competing pathways, i.e., global unfolding in the core region and partial openings of the native state, determine the observed exchange rates. These findings are analyzed with respect to the amyloidogenic properties of the protein.