2E9W: Crystal Structure Of The Extracellular Domain Of Kit In Complex With Stem Cell Factor (Scf)

Citation:
Abstract
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.
PDB ID: 2E9WDownload
MMDB ID: 53016
PDB Deposition Date: 2007/1/27
Updated in MMDB: 2007/11
Experimental Method:
x-ray diffraction
Resolution: 3.5  Å
Source Organism:
Similar Structures:
Biological Unit for 2E9W: tetrameric; determined by author
Molecular Components in 2E9W
Label Count Molecule
Proteins (4 molecules)
2
Mast/stem Cell Growth Factor Receptor(Gene symbol: KIT)
Molecule annotation
2
KIT Ligand(Gene symbol: KITLG)
Molecule annotation
Chemicals (6 molecules)
1
6
* Click molecule labels to explore molecular sequence information.

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