Poster Presentation The 46th Lorne Conference on Protein Structure and Function 2021

Investigating the interaction between JAK1 FERM-SH2 and box 1 of class II cytokine receptors (#216)

Amarachi Amah 1 2 , Jason Brouwer 1 2 , Nadia Kershaw 1 2 , Jeff Babon 1 2
  1. Walter and Eliza Hall institute, Parkville, Victoria, Australia
  2. Medical biology, University of Melbourne , Parkville, Victoria, Australia

The association between Janus kinase 1 (JAK1) and the intracellular domain of cytokine receptors is essential for cytokine signalling. JAK1 binds to specific sites termed box 1 and 2 on the intracellular domain of cytokine receptors through its FERM-SH2 domain. Structural analysis revealed that JAK1 FERM-SH2 binds predominantly to box 1 of interferon lambda receptor 1 (IFNLR1), a class II cytokine receptor. The motif “PxxLxF” in IFNLR1 box 1 was essential for its interaction with JAK1 FERM-SH2. Sequence alignment revealed that PxxLxF motif was conserved in the box 1 of other class II cytokine receptors such as IL10RA, IL20RA, IL22RA1, IFNAR2 and IFNGR1. However, no study has investigated the binding of JAK1 FERM-SH2 to box 1 of these class II cytokine receptors. This study aims to investigate the interaction between JAK1 FERM-SH2 and peptides containing box 1 of class II cytokine receptors using receptor-ligand binding assays. We have shown that JAK1 FERM-SH2 binds weakly to the box 1 of class II cytokine receptors containing the PxxLxF motif. In conclusion, we have shown that although PxxLxF is conserved in box 1 of some class II cytokine receptors, it is not essential for the receptor’s interaction with JAK1 FERM-SH2. Future studies would involve investigating the interaction between JAK1 FERM-SH2 and box 1 and 2 of class II cytokine receptors. 

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