A Disorder-Induced Domino-Like Destabilization Mechanism Governs the Folding and Functional Dynamics of the Repeat Protein IκBα
Figure 5
Folding landscape and complexity.
(A) SSA free-energy landscape of ligand-free IκBα highlighting the diversity of intermediates (lower free energy – FE - and blue in color) that can be populated during folding. The coordinates (m, n) represent the starting residue and the number of structured residues, respectively. The fully folded state is therefore (1, 213), i.e. starting from 1 there are 213 folded residues, while a partially structured state with ARs 2, 3, and 4 folded will be centered around (35, 90), i.e. starting from 35 there are 90 structured residues. The partially folded repeats in each of the local minima are indicated as numbers within ellipses following the color code of Figure 1A. (B) Structural view of the intermediates I1 and I2. The black curves indicate unstructured regions.