title: Crystal structure of human stem cell factor: implication for stem cell factor receptor dimerization and activation.
abstract: Stem cell factor (SCF) plays important roles in hematopoiesis and the survival, proliferation, and differentiation of mast cells, melanocytes, and germ cells. SCF mediates its biological effects by binding to and activating a receptor tyrosine kinase designated c-kit or SCF receptor. In this report we describe the 2.3-A crystal structure of the functional core of recombinant human SCF. SCF is a noncovalent homodimer composed of two slightly wedged protomers. Each SCF protomer exhibits an antiparallel four-helix bundle fold. Dimerization is mediated by extensive polar and nonpolar interactions between the two protomers with a large buried surface area. Finally, we have identified a hydrophobic crevice and a charged region at the tail of each protomer that functions as a potential receptor-binding site. On the basis of these observations, a model for SCF small middle dotc-kit complex formation and dimerization is proposed.
authors.affiliation: Departments of Pharmacology and Biochemistry and Skirball Institute, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Joachimiak
authors.forename: J
authors.initials: J
authors.lastname: Schlessinger
authors.forename: X P
authors.initials: XP
authors.lastname: Kong
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019009:Proto-Oncogene Proteins c-kit / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D019089:Stem Cell Factor / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit