2e9w: Difference between revisions
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|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene> | |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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= KIT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), SCF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= KIT ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), SCF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1exz|1EXZ]], [[2ec8|2EC8]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2e9w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e9w OCA], [http://www.ebi.ac.uk/pdbsum/2e9w PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2e9w RCSB]</span> | |||
}} | }} | ||
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==Disease== | ==Disease== | ||
Known | Known disease associated with this structure: Gastrointestinal stromal tumor, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]], Germ cell tumors OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]], Leukemia, acute myeloid OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]], Mast cell leukemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]], Mastocytosis with associated hematologic disorder OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]], Piebaldism OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164920 164920]], Skin/hair/eye pigmentation 7, blond/brown hair OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=184745 184745]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Yuzawa, S.]] | [[Category: Yuzawa, S.]] | ||
[[Category: Zhang, Z.]] | [[Category: Zhang, Z.]] | ||
[[Category: dimerization]] | [[Category: dimerization]] | ||
[[Category: glycoprotein]] | [[Category: glycoprotein]] | ||
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[[Category: transferase/hormone complex]] | [[Category: transferase/hormone complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:45:55 2008'' | ||
Revision as of 02:45, 31 March 2008
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| , resolution 3.50Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | KIT (Homo sapiens), SCF (Homo sapiens) | ||||||
| Activity: | Receptor protein-tyrosine kinase, with EC number 2.7.10.1 | ||||||
| Related: | 1EXZ, 2EC8
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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 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 StructureAbout this Structure
2E9W is a Protein complex structure of sequences 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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