Structure of the active core of human stem cell factor and analysis of binding to its receptor Kit
| Autor: | Ogan Gurel, Rashid Syed, Wayne A. Hendrickson, Hsieng Sen Lu, Xuliang Jiang, Elizabeth A. Mendiaz, Osslund Timothy D, Keith Langley, Christi L. Clogston, George Stearns |
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| Rok vydání: | 2000 |
| Předmět: |
Models
Molecular Protein Conformation medicine.medical_treatment Molecular Sequence Data Stem cell factor Plasma protein binding General Biochemistry Genetics and Molecular Biology Receptor tyrosine kinase medicine Humans Amino Acid Sequence Binding site Receptor Molecular Biology Stem Cell Factor Sequence Homology Amino Acid General Immunology and Microbiology biology General Neuroscience Growth factor Articles Molecular biology Recombinant Proteins Proto-Oncogene Proteins c-kit embryonic structures biology.protein Biophysics Cytokines Dimerization Platelet-derived growth factor receptor Protein Binding |
| Zdroj: | The EMBO Journal. 19:3192-3203 |
| ISSN: | 1460-2075 |
| DOI: | 10.1093/emboj/19.13.3192 |
| Popis: | 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 Å 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. |
| Databáze: | OpenAIRE |
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