2ec8
From Proteopedia
(New page: 200px<br /> <applet load="2ec8" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ec8, resolution 3.00Å" /> '''Crystal structure o...) |
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caption="2ec8, resolution 3.00Å" /> | caption="2ec8, resolution 3.00Å" /> | ||
'''Crystal structure of the exctracellular domain of the receptor tyrosine kinase, Kit'''<br /> | '''Crystal structure of the exctracellular domain of the receptor tyrosine kinase, Kit'''<br /> | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known diseases 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]] | ||
==About this Structure== | ==About this Structure== | ||
| - | 2EC8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http:// | + | 2EC8 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2EC8 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 14:15:18 2008'' |
Revision as of 12:15, 23 January 2008
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Crystal structure of the exctracellular domain of the receptor tyrosine kinase, Kit
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.
About this Structure
2EC8 is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Receptor protein-tyrosine kinase, with EC number 2.7.10.1 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
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