2ec8: Difference between revisions
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[[Image:2ec8.jpg|left|200px]] | [[Image:2ec8.jpg|left|200px]] | ||
'''Crystal structure of the exctracellular domain of the receptor tyrosine kinase, Kit''' | {{Structure | ||
|PDB= 2ec8 |SIZE=350|CAPTION= <scene name='initialview01'>2ec8</scene>, resolution 3.00Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Receptor_protein-tyrosine_kinase Receptor protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.1 2.7.10.1] | |||
|GENE= KIT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Crystal structure of the exctracellular domain of the receptor tyrosine kinase, Kit''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2EC8 is a [ | 2EC8 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EC8 OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17662946 17662946] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Receptor protein-tyrosine kinase]] | [[Category: Receptor protein-tyrosine kinase]] | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 16:38:11 2008'' | ||
Revision as of 17:38, 20 March 2008
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| , resolution 3.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | KIT (Homo sapiens) | ||||||
| Activity: | Receptor protein-tyrosine kinase, with EC number 2.7.10.1 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of the exctracellular domain of the receptor tyrosine kinase, Kit
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
2EC8 is a Single protein structure of sequence from Homo sapiens. 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
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