Table 2 Properties of disorder in C1CRs
From: Orchestration of signaling by structural disorder in class 1 cytokine receptors
IDP characteristic | Key descriptors for C1CR ICDs |
|---|---|
Specific amino acid composition | The C1CR-ICDs have a unique amino acid composition that distinguishes them from both folded proteins and IDPs. Depleted in Met, Arg, Ala, and Lys compared to folded proteins and IDPs Enriched in Cys, Trp, Leu and Val compared to IDPs Highly enriched in Pro compared to folded proteins and IDPs |
Disordered | All the ICDs of the C1CRs are predicted disordered throughout their sequences, but has been shown experimentally only for the GHR and PRLR |
Rich in SLiMs | #Several SLiMs are common to groups of the C1CRs, in particular • BOX1 motifs (JAK/SH2) ΦΦP.ΦP.P (JAK2) ΦP. P (JAK1) ΦΦP.ΦP.[P/Φ].[P/Φ](JAK3/TYK2) • 14–3-3 R[^DE](0,2)[^DEPG][ST][^PRIKGN]-P R[^DE](0,2)[^DEPG][ST][^P]* • SOCS2/3 pY [AFILVWY].[AFILVWY] (loose SH2-motif) • PDZ ..[ST].[ACVILF]* (Class 1) ..[VLIFY].[ACVILF]* (Class 2) ..[DE].[ACVILF]* (Class 3) • TRAF2/6 [PSAT].[QE] E (TRAF2) [P].[Q]..D (TRAF2) [P].[Q]..[FYWHDE] (TRAF6) • STAT [Y]..[P] (STAT1) [Y]..[Q] (STAT3) [Y][VLTFIC].. (STAT5) (promiscuous) [Y]..[F] (STAT6) • Phospho-degrons D [S]G.(2,3[ST] [LIVMP].(0,2)(T)P..[ST] • Dileucine motifs [D/E]...[L/I][L/I] [D/E]..LL • Tyrosine-based internalization motifs Y..[LMVIF] Only very few SLiMs have been addressed experimentally and only 7 three-dimensional structures exist of complexes. |
Rich in PTMs | All C1CR-ICDs have numerous predicted phosphorylation sites distributed along the chain, but only few have been confirmed by MS or by mutational studies. Some SLiMs are regulated by phosphorylation |
Alternative splice variants | Out of a total of 29 C1CRs, 16 have at least two isoforms differing in their ICDs, but up to five ICD isoforms are seen for some receptors (PRLR, IL-31R). Isoforms allow for network rewiring by insertion and deletion of specific SLiMs |
Dynamic conformational ensemble | The CIDER analysis and measured Rg of presentative C1CR-ICDs suggest that they take on a slightly compacted, but dynamic ensemble |
Multispecificity | Overlapping SLiMs dominates C1CR-ICDs and allow competition as a regulatory mechanism. This is made possible as the disordered chain can adapts to several different binding partner. |