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Sequence-based prediction of protein binding mode landscapes
Fig 4
Prediction of context-dependent regions by the FuzPred method.
(A) Prediction of binding mode profiles. Comparable probabilities for disorder-to-order transition (pDO, dark gray) and disorder-to-disorder transition (pDD, light gray) indicate a disordered binding mode for the region of residues 45–55 (grey box), which involves both the docking and the KIS motif, consistently with the experimental data [33] (top panel). Based on the binding profile, this region can fluctuate between ordered and disordered interactions (bottom panel), which will depend on the signaling pathway. The 
values indicate that both the docking motifs and the N-terminal part of the KIS domain are capable to establish different binding modes, consistent with their involvement in disordered interactions. Selected MKK4 conformers docked onto p38α structure (PDB:1lew). The docking motif (marine) and the KIS domain (light blue) are shown (coordinates as a courtesy of Dr. Malene Ringkjobing-Jensen). (B) Prediction of phosphorylation-induced folding. Trans-autophosphorylation induces folding of the activation loop in the dual-activity enzyme Ire1, which promotes its oligomerisation [19]. Packing of four monomers (wheat, light blue, pale green and light pink surfaces) (PDB: 3fbv) are stabilised by the ordered activation loop (cartoon, the phosphorylated Ser841 is shown by spheres). FuzPred predicts slightly higher probabilities for disorder-to-order transition (pDO, dark gray, top panel) for the activation loop (grey box) than for disorder-to-disorder transition (pDD, light gray, top panel), indicating that it can fold upon binding. The high 
values (bottom panel) corroborate that the activation loop can sample both disordered and ordered states in the bound form, which could be shifted towards the folded form by phosphorylation.
doi: https://doi.org/10.1371/journal.pcbi.1007864.g004