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Structure of the active core of human stem cell factor and analysis of binding to its receptor Kit
Author(s) -
Jiang Xuliang,
Gurel Ogan,
Mendiaz Elizabeth A.,
Stearns George W.,
Clogston Christi L.,
Lu Hsieng S.,
Osslund Timothy D.,
Syed Rashid S.,
Langley Keith E.,
Hendrickson Wayne A.
Publication year - 2000
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/19.13.3192
Subject(s) - george (robot) , library science , management , history , art history , computer science , economics
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.