Fig. 3
The kinase inhibitory region acts as a pseudosubstrate. a Molecular details of the interaction between the SOCS1 kinase inhibitory region (red) and JAK1 (beige). The interaction is driven by six continuous residues in the SOCS1 KIR (His54 to Arg59), these primarily interact with the activation loop, GQM motif and glycine-rich loop of JAK1. Black dashed lines indicate hydrogen-bonds whilst grey dotted lines are van der Waals contacts. b A model of a peptide substrate (green) bound to the JAK1 kinase domain (based on the insulin receptor kinase/substrate structure (PDB: 1IRK)) indicates that the SOCS1 KIR acts as a pseudosubstrate with His54 mimicking the substrate tyrosine. c The GQM motif (Gly1097, Gln1098, Met1099) in JAK1 is a primary interaction site with SOCS1 and contacts the KIR, extended SH2 subdomain and SH2 domain (particularly the BC loop). d IC50 values of SOCS1 KIR mutants indicate that each residue of the KIR contributes to the affinity of the interaction. Errors are standard error of the mean from two independent experiments. e Sequence alignment of the KIR of SOCS1 from various species shows a high level of sequence conservation
