5VE6

Crystal structure of Sugen kinase 223

Summary for 5VE6

• Entry DOI: 10.2210/pdb5ve6/pdb
• Descriptor: Tyrosine-protein kinase SgK223 (2 entities in total)
• Functional Keywords: kinase, pseudokinase, signaling protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 54230.04

Authors

Patel, O.,Lucet, I.,Panjikar, S. (deposition date: 2017-04-03, release date: 2017-10-18, Last modification date: 2024-03-06)

Primary citation

Patel, O.,Griffin, M.D.W.,Panjikar, S.,Dai, W.,Ma, X.,Chan, H.,Zheng, C.,Kropp, A.,Murphy, J.M.,Daly, R.J.,Lucet, I.S.
Structure of SgK223 pseudokinase reveals novel mechanisms of homotypic and heterotypic association.
Nat Commun, 8:1157-1157, 2017

PubMed Abstract: 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.

PubMed: 29079850
DOI: 10.1038/s41467-017-01279-9

Experimental method

X-RAY DIFFRACTION (2.953 Å)