Figure 7.

Global fitting analysis of the concentration dependent TTR reassembly time courses. A) Global fitting analysis of the TTR reassembly kinetics to Mechanism C. The fits (red lines) do not accurately predict the kinetics of TTR homotetramer reassembly (black circles). B) Global fitting analysis of the TTR reassembly kinetics to Mechanism D. At low protein concentrations, the mechanistic fitting analysis (red lines) accurately predict the reassembly time courses (black symbols), but as the concentration of protein increases, the predicted fits are found to be poor, demonstrating that TTR homotetramers do not reassemble by Mechanism D. C) Global fitting analysis of TTR reassembly kinetics to Mechanism E. Mechanism E accurately predicts the reassembly time courses over the entire range of protein concentrations indicating that TTR tetramers reassemble by this mechanistic pathway. Fitting the concentration dependent reassembly kinetics to more complicated variations of Mechanism E (e.g. incorporating first order reorganization steps or allowing the existence of a second type of dimeric species) does not substantially improve the fit.