IDPs and their complexes in GPCR and nuclear receptor signaling

Structural Insights into the Interaction of the Intrinsically Disordered Co-activator TIF2 with Retinoic Acid Receptor Heterodimer (RXR/RAR)

“…Similar motifs (LxxI/HIxxI/L, called CoRNR-boxes) are identified in co-repressors [15][16][17]. Importantly, NRIDs are mainly intrinsically disordered regions with pre-formed secondary structure elements corresponding to NR-and CoRNR-boxes [18][19][20][21].…”

Structural Insights into the Intrinsically Disordered GPCR C-Terminal Region, Major Actor in Arrestin-GPCR Interaction

“…Conversely, the extracellular regions (N-terminal and C-terminal domains and loops) are rather diversified in length and sequence [4] and are involved in the functional properties of GPCRs, such as, respectively, ligand and partner binding. It is interesting to note that theses extracellular regions are predicted to contain intrinsically disordered regions (IDRs) [5,6], which could play key roles in GPCR interaction (for review [68,69]). Indeed, IDRs explore an astronomical number of conformations in solution that we assume in fast equilibrium, and very often contain pre-formed secondary structure elements.…”

Phosphorylation motif dictates GPCR C-terminal domain conformation and arrestin interaction

“…Interestingly, the GPCR C-terminal domain presents all the structural, dynamic and functional characteristics of an intrinsically disordered region (IDR) (Dunker et al, 2001; Guillien et al, 2020; Uversky et al, 2000; Zhou et al, 2018). Intrinsically disordered proteins (IDPs) or IDRs are highly flexible with a low content of secondary structure, whose specific role in fundamental signaling and regulation processes started to be revealed two decades ago (Kriwacki et al, 1996; Olsen et al, 2017; Wright and Dyson, 2015).…”