Structure of SgK223 pseudokinase reveals novel mechanisms of homotypic and heterotypic association

Onisha Patel, Michael D.W. Griffin, Santosh Panjikar, Weiwen Dai, Xiuquan Ma, Howard Chan, Celine Zheng, Ashleigh Kropp, James M. Murphy, Roger J. Daly, Isabelle S. Lucet

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28 Citations (Scopus)


The mammalian pseudokinase SgK223, and its structurally related homologue SgK269, are oncogenic scaffolds that nucleate the assembly of specific signalling complexes and regulate tyrosine kinase signalling. Both SgK223 and SgK269 form homo- and hetero-oligomers, a mechanism that underpins a diversity of signalling outputs. However, mechanistic insights into SgK223 and SgK269 homo- and heterotypic association are lacking. Here we present the crystal structure of SgK223 pseudokinase domain and its adjacent N- and C-terminal helices. The structure reveals how the N- and C-regulatory helices engage in a novel fold to mediate the assembly of a high-affinity dimer. In addition, we identified regulatory interfaces on the pseudokinase domain required for the self-assembly of large open-ended oligomers. This study highlights the diversity in how the kinase fold mediates non-catalytic functions and provides mechanistic insights into how the assembly of these two oncogenic scaffolds is achieved in order to regulate signalling output.

Original languageEnglish
Article number1157
Number of pages15
JournalNature Communications
Issue number1
Publication statusPublished - 1 Dec 2017


  • cancer
  • kinases
  • x-ray crystallography

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