Poster Presentation The 43rd Lorne Conference on Protein Structure and Function 2018

Crystal Structure of the SH2 Domain of the Lypmphocyte Adaptor Protein LNK (SH2B3) (#216)

Rhiannon Morris 1 , Nadia Kershaw 1 , Douglas Hilton 1 , Jeff Babon 1
  1. Walter and Eliza Hall Institute of medical research, Parkville, VIC, Australia

Maintenance of the haematopoietic system is controlled by intercellular signalling molecules known as cytokines which function by activating the JAK-STAT pathway in their target cells. The tight regulation of this pathway is critical for maintenance of homeostasis in the haematopoietic and immune systems. The adaptor protein LNK (SH2B3) is involved in the negative regulation of JAK2 activity in the context of erythropoietin and thrombopoietin signalling. It is known that the SH2 domain of LNK binds to the pY813 residue in JAK2 with high affinity, however the interaction between these proteins has not yet been visualised. We have solved the first structure of the LNK SH2 domain bound to a JAK2 pY813 peptide. Our structure demonstrates how the SH2 domain recognises its substrate and provides an insight into the mechanism of JAK2 regulation by LNK.