Crystal structure of human stem cell factor: Implication for stem cell factor receptor dimerization and activation

Stem cell factor (SCF) plays important roles in hematopoiesis and the survi val, proliferation, and differentiation of mast cells, melanocytes, and ger m 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-Angstrom crystal structure of the functional core of re combinant human SCF, SCF is a noncovalent homodimer composed of two slightl y wedged protomers. Each SCF protomer exhibits an antiparallel four-helix b undle fold. Dimerization is mediated by extensive polar and nonpolar intera ctions 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 th e basis of these observations, a model for SCFc-kit complex formation and d imerization is proposed.