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2o26
From Proteopedia
(New page: 200px<br /><applet load="2o26" size="450" color="white" frame="true" align="right" spinBox="true" caption="2o26, resolution 2.50Å" /> '''Structure of a class...) |
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| - | [[Image:2o26.gif|left|200px]]<br /><applet load="2o26" size=" | + | [[Image:2o26.gif|left|200px]]<br /><applet load="2o26" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2o26, resolution 2.50Å" /> | caption="2o26, resolution 2.50Å" /> | ||
'''Structure of a class III RTK signaling assembly'''<br /> | '''Structure of a class III RTK signaling assembly'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Stem cell factor (SCF) binds to and activates the KIT receptor, a class | + | 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 Structure== | ==About this Structure== | ||
| - | 2O26 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. 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:// | + | 2O26 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. 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=2O26 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Receptor protein-tyrosine kinase]] | [[Category: Receptor protein-tyrosine kinase]] | ||
[[Category: Chen, X.]] | [[Category: Chen, X.]] | ||
| - | [[Category: Focia, P | + | [[Category: Focia, P J.]] |
[[Category: He, X.]] | [[Category: He, X.]] | ||
[[Category: Liu, H.]] | [[Category: Liu, H.]] | ||
| Line 26: | Line 26: | ||
[[Category: stem cell factor]] | [[Category: stem cell factor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:13:36 2008'' |
Revision as of 16:13, 21 February 2008
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Structure of a class III RTK signaling assembly
Overview
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 Structure
2O26 is a Protein complex structure of sequences from Mus musculus. Active as Receptor protein-tyrosine kinase, with EC number 2.7.10.1 Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Thu Feb 21 18:13:36 2008
