Description
Experimental Technique/Method:X-RAY DIFFRACTION
Resolution:2.5
Classification:CYTOKINE/SIGNALING PROTEIN
Release Date:2007-03-13
Deposition Date:2006-11-29
Revision Date:2008-05-01#2011-07-13
Molecular Weight:199793.89
Macromolecule Type:Protein
Residue Count:1740
Atom Site Count:13374
DOI:10.2210/pdb2o26/pdb
Abstract:
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.
Resolution:2.5
Classification:CYTOKINE/SIGNALING PROTEIN
Release Date:2007-03-13
Deposition Date:2006-11-29
Revision Date:2008-05-01#2011-07-13
Molecular Weight:199793.89
Macromolecule Type:Protein
Residue Count:1740
Atom Site Count:13374
DOI:10.2210/pdb2o26/pdb
Abstract:
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.
| Date made available | 2007 |
|---|---|
| Publisher | RCSB-PDB |