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Sequential four-state mechanism involving two partially structured ensembles, I1 and I2, in addition to the acid-unfolded (U) and native (N) states. Cartoons of the different states are consistent with the fraction of helical residues (fH) and radius of gyration (Rg) reported in ref. 3. Cylinders indicate the approximate position of α-helices in the native state and possible arrangement of core helices in the intermediates consistent with amide protection data (17).
