2e9w
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Crystal structure of the extracellular domain of Kit in complex with stem cell factor (SCF)
OverviewOverview
Stem Cell Factor (SCF) initiates its multiple cellular responses by, binding to the ectodomain of KIT, resulting in tyrosine kinase activation., We describe the crystal structure of the entire ectodomain of KIT before, and after SCF stimulation. The structures show that KIT dimerization is, driven by SCF binding whose sole role is to bring two KIT molecules, together. Receptor dimerization is followed by conformational changes that, enable lateral interactions between membrane proximal Ig-like domains D4, and D5 of two KIT molecules. Experiments with cultured cells show that KIT, activation is compromised by point mutations in amino acids critical for, D4-D4 interaction. Moreover, a variety of oncogenic mutations are mapped, to the D5-D5 interface. Since key hallmarks of KIT structures, ligand-induced receptor dimerization, and the critical residues in the, D4-D4 interface, are conserved in other receptors, the mechanism of KIT, stimulation unveiled in this report may apply for other receptor, activation.
DiseaseDisease
Known diseases associated with this structure: Gastrointestinal stromal tumor, somatic OMIM:[164920], Germ cell tumors OMIM:[164920], Leukemia, acute myeloid OMIM:[164920], Mast cell leukemia OMIM:[164920], Mastocytosis with associated hematologic disorder OMIM:[164920], Piebaldism OMIM:[164920]
About this StructureAbout this Structure
2E9W is a Protein complex structure of sequences from Homo sapiens with NAG as ligand. Active as Receptor protein-tyrosine kinase, with EC number 2.7.10.1 Full crystallographic information is available from OCA.
ReferenceReference
Structural Basis for Activation of the Receptor Tyrosine Kinase KIT by Stem Cell Factor., Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J, Cell. 2007 Jul 27;130(2):323-34. PMID:17662946
Page seeded by OCA on Mon Nov 12 21:47:18 2007