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Fig. 4. Multifaceted allosteric coupling mediated by IDRs in macromolecular complexes. (A) A schematic illustration is shown for a hypothetical energy landscape of the ensemble of a multiprotein complex in which three protein subunits (orange cone, purple sphere, and green polyhedron) are bound to distinct linear motifs embedded in an IDR of the hub protein. Four different states of the complex are shown with similar free energy levels and low activation energy barriers among them (i.e., flat energy landscape). Each state exhibits a unique conformation determined by the binding affinities of the protein subunits and the cooperativities among them. Hypothetical (positive or negative) cooperativities were assigned to each state as shown in the appended schematic table. In the absence of external signals (protein binding, PTMs), state 1 is marginally more stable than others. (B-D) Upon binding of different external proteins (green torus, yellow cube, and purple cylinder) to the distinct regulatory sites on the IDR, the ensemble population shifts toward the specific conformational/functional states (state 2-4). Such a multifaceted allosteric shift is energy-efficient and fast due to the preconditioned heterogeneity and low energy barriers in the ensemble. (E) Hypothetical allosteric transition in an ordered protein in which two end states greatly differ in free energy level.
Mol. Cells 2020;43:899~908 https://doi.org/10.14348/molcells.2020.0186
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