Sequence-based prediction of protein binding mode landscapes
Fig 1
Illustration and assignment of binding modes.
(A) Binding modes considered in this work. Binding modes are shown for the interferon-induced, double-stranded RNA-activated protein kinase (RPK). The activation segment (residues 440–450) is not visible in the crystal structure of the monomeric form (PDB: 6d3l [52]), and remains disordered in the dimeric form (PDB: 3uiu, 6d3k). This binding mode represents a disorder-to-disorder transition. Interactions with eukaryotic initiation factor 2 (eIF2), however, triggers folding of the activation segment to mediate inter-molecular contacts (PDB:2a1a [53]), which process is coupled to auto-phosphorylation of Thr446. The RPK binding to eIF2 is classified as a disorder-to-order transition. (B) Assignment of context-dependent binding. Structures corresponding to the same sequence (P19525, residues 440–460) were collected in the monomeric and complex forms. Residues were observed (O) in the crystal structures were assigned as 'ordered', missing residues (M) were assigned as disordered. 'Context-dependent' residues (blue bar) were disordered in the monomeric form, but were represented both in ordered and disordered forms in different complexes. 'Disorder-to-order' residues were disordered in the monomeric structure and ordered (O) in all complexes; whereas 'disorder-to-disorder' residues also remained to be disordered (M) in all bound state structures.