2e9w
From Proteopedia
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'''Crystal structure of the extracellular domain of Kit in complex with stem cell factor (SCF)''' | '''Crystal structure of the extracellular domain of Kit in complex with stem cell factor (SCF)''' | ||
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[[Category: Yuzawa, S.]] | [[Category: Yuzawa, S.]] | ||
[[Category: Zhang, Z.]] | [[Category: Zhang, Z.]] | ||
| - | [[Category: | + | [[Category: Dimerization]] |
| - | [[Category: | + | [[Category: Glycoprotein]] |
| - | [[Category: | + | [[Category: Growth factor cytokine]] |
| - | [[Category: | + | [[Category: Receptor tyrosine kinase]] |
| - | [[Category: | + | [[Category: Transferase/hormone complex]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 02:12:53 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 23:12, 3 May 2008
Crystal structure of the extracellular domain of Kit in complex with stem cell factor (SCF)
Contents |
Overview
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.
Disease
Known disease 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], Skin/hair/eye pigmentation 7, blond/brown hair OMIM:[184745]
About this Structure
2E9W is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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 Sun May 4 02:12:53 2008
