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

نویسندگان

  • Z Zhang
  • R Zhang
  • A Joachimiak
  • J Schlessinger
  • X P Kong
چکیده

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.

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عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 97 14  شماره 

صفحات  -

تاریخ انتشار 2000