Fig. 4.

The rate of urea-mediated (6 M) tetramer dissociation for WT (A) (green circles), V122I (B), and V30M (C) TTR in the absence of small molecules. TTR dissociation is slowed dramatically when WT and the variants are preincubated with genistein. Far-UV CD ellipticity integrated over 214–218 nm at two concentrations of genistein (1.8 μM, ▴; 3.6 μM, ♦) was compared with that of TTR (WT or variant, 1.8 μM) without genistein to determine the fraction of TTR that dissociated and rapidly unfolded at each time point. As a reference, WT TTR tetramer dissociation occurs with a first-order rate constant of 0.033 h^-1 under these conditions.