Reconciling binding mechanisms of intrinsically disordered proteins

Introducing Protein Intrinsic Disorder

“…A brief description of such a consensus mechanism from ref. 226 is provided (Fig. 18): the first step can be described as the non-specific reeling of the IDP by its target molecule via a "flycasting" mechanism.…”

“…The driving force of binding is provided by both the favorable intermolecular interaction energy and restriction of conformational entropy by binding conformationally restricted PSEs. 226 An excellent example studied by NMR and MD experiments is the pKID and CBP complex formation. 227,228 It is of note, however, that in some complexes the binding does not induce folding.…”

Predicting intrinsic disorder in proteins: an overview

“…An alternative idea was that binding of disordered regions depends on conformational selection from the structural ensemble [14] perhaps via "pre-formed elements" [15] that dominate the ensemble. Recently, it has been suggested that protein-protein interactions actually involve a combination of coupled binding and folding and conformational selection [16]. With regard to protein-protein interactions, papers have appeared recently that follow the structural transitions as these highly flexible regions associate with their partners [17].…”

The SCHOOL of nature: II. Protein order, disorder, and oligomericity in transmembrane signaling

“…Another scenario, the "conformational selection" model, in which IDPs bind and fully fold through conformational selection following a two-state model, has been also proposed. [68][69][70] In the consensus synergistic model, 68 conformational selection has been proposed to play the most important role in the specific encounter, while coupled folding and binding has been suggested to be essential for the formation of the fully-bound complexes. Recently discovered functionally relevant binding of IDPs to unfolded and folded proteins without folding on the interacting partner [9][10][11]60 revealed a novel insight into IDP interactions, thus demonstrating the existence of two different modes of IDP binding to their protein partners: with and without folding (the "disorder-to-order" and "no disorder-to-order" scenarios).…”