Intrinsic Protein Disorder and Protein-Protein Interactions

Abstract

Intrinsically disordered proteins often bind to more than one partner. In this study, we focused on 11 sets of complexes in which the same disordered segment becomes bound to two or more distinct partners. For this collection of protein complexes, two or more partners of each disordered segment were selected to have less than 25% amino acid identity at structurally aligned positions. As it turned out that most of the examples so selected had similar 3D structure, the studied set was reduced to just these similar-fold cases. Based on the analyses of the interacting partners, the average sequence identity of the partners' binding regions showed substantially higher conservation as compared to the nonbinding regions: The residue identities, averaged over the 11 sets of partner proteins, were as follows: binding residues, 42 ± 6%; nonbinding residues 20 ± 3%; nonbinding buried residues 26 ± 5%; and nonbinding surface residues 16 ± 3% . The higher sequence identity of the binding residues compared to the other sets of residues provides evidence that these observed interactions are likely to be meaningful biological interactions, not artifacts. Since many of the features of the various interactions indicate that the disordered binding segments were likely to have been disordered before binding, these results also add further weight to the existence and function of intrinsically disordered regions inside cells.

The human RBPome: From genes and proteins to human disease

“…Intrinsically disordered proteins are known to be highly interacting due to their unstable 3D structure and hence form hubs in their protein-protein interaction networks [44,46,47]. This property of disordered proteins being hubs in their protein-protein interaction network has been analysed in our current study.…”

Exploring the binding diversity of intrinsically disordered proteins involved in one‐to‐many binding

“…[57][58][59][60][61] Other detailed investigation into the MoRFs with similar-fold partners was performed and discussed in our previous work. 52 …”

“…48 With regard to the former, we likewise know of just three published examples: namely, a short segment from HIF1a bound to two partners, the TAZ1 domain and the asparagine hydroxylase FIH protein, 30 a short segment from the C-terminus of p53 bound to four partners, S100bb, sirtuin, CREB binding protein, and cyclin A2, 48 and a larger collection of various short segments bound to multiple partners. 52 We have carried out data mining on the Protein Data Bank (PDB) to find additional examples of both one-to-many and many-to-one complexes at atomic resolution. While both datasets are assembled, our focus herein is on the collected examples of one-to-many interactions.…”

Resilience of death: intrinsic disorder in proteins involved in the programmed cell death

“…27 The complexity of the disorderbased interactomes is further increased due to the ability of a single IDPR to bind to multiple partners gaining potentially very different structures in the bound state. 28 Because of their critically important roles in regulation, signaling, and control pathways, misbehavior of IDPs is commonly associated with the pathogenesis of various diseases. 29 Since IDPs are 'control freaks', they commonly act as important regulators of protein-protein interaction networks.…”