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- Title
Structure of the active core of human stem cell factor and analysis of binding to its receptor kit.
- Authors
Jiang, X; Gurel, O; Mendiaz, E A; Stearns, G W; Clogston, C L; Lu, H S; Osslund, T D; Syed, R S; Langley, K E; Hendrickson, W A
- Abstract
Stem cell factor (SCF) is an early-acting hematopoietic cytokine that elicits multiple biological effects. SCF is dimeric and occurs in soluble and membrane-bound forms. It transduces signals by ligand- mediated dimerization of its receptor, Kit, which is a receptor tyrosine kinase related to the receptors for platelet-derived growth factor (PDGF), macrophage colony-stimulating factor, Flt-3 ligand and vascular endothelial growth factor (VEGF). All of these have extracellular ligand-binding portions composed of immunoglobulin-like repeats. We have determined the crystal structure of selenomethionyl soluble human SCF at 2.2 A resolution by multiwavelength anomalous diffraction phasing. SCF has the characteristic helical cytokine topology, but the structure is unique apart from core portions. The SCF dimer has a symmetric 'head-to-head' association. Using various prior observations, we have located potential Kit-binding sites on the SCF dimer. A superimposition of this dimer onto VEGF in its complex with the receptor Flt-1 places the binding sites on SCF in positions of topographical and electrostatic complementarity with the Kit counterparts of Flt-1, and a similar model can be made for the complex of PDGF with its receptor.
- Publication
The EMBO journal, 2000, Vol 19, Issue 13, p3192
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1093/emboj/19.13.3192