2o26
Structure of a class III RTK signaling assembly
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| , resolution 2.50Å | |||||||
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| Ligands: | , , , | ||||||
| Gene: | Kitlg, Kitl, Mgf, Sl, Slf (Mus musculus), Kit, Sl (Mus musculus) | ||||||
| Activity: | Receptor protein-tyrosine kinase, with EC number 2.7.10.1 | ||||||
| Related: | 2O27
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
OverviewOverview
Stem cell factor (SCF) binds to and activates the KIT receptor, a class III receptor tyrosine kinase (RTK), to stimulate diverse processes including melanogenesis, gametogenesis and hematopoeisis. Dysregulation of KIT activation is associated with many cancers. We report a 2.5 A crystal structure of the functional core of SCF bound to the extracellular ligand-binding domains of KIT. The structure reveals a 'wrapping' SCF-recognition mode by KIT, in which KIT adopts a bent conformation to facilitate each of its first three immunoglobulin (Ig)-like domains to interact with SCF. Three surface epitopes on SCF, an extended loop, the B and C helices, and the N-terminal segment, contact distinct KIT domains, with two of the epitopes undergoing large conformational changes upon receptor binding. The SCF/KIT complex reveals a unique RTK dimerization assembly, and a novel recognition mode between four-helix bundle cytokines and Ig-family receptors. It serves as a framework for understanding the activation mechanisms of class III RTKs.
About this StructureAbout this Structure
2O26 is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases., Liu H, Chen X, Focia PJ, He X, EMBO J. 2007 Feb 7;26(3):891-901. Epub 2007 Jan 25. PMID:17255936
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