Description

Stem cell factor (SCF) is a recently identified homodimeric hematopoietic growth factor that acts to stimulate the proliferation of early hematopoietic stem cells.1 Comparative analysis of the SCF sequence has revealed that it is similar to a number of other growth factors such as GM-CSF, growth hormone, IL-4 and M-CSF for which recent structural results have shown a distinctive 4 *-helix folding motif. We report here preliminary crystallographic studies enroute to obtaining more detailed structural information about this protein. Several different crystal forms of SCF were grown of which the orthorhombic form (a=88.1, b=83.4, c=72.7) diffracted stably to 2.8Å spacings; the presence of calcium and stabilization at a pH slightly lower than the pH during crystal growth was absolutely required for the production of diffraction quality crystals. Area detector data were collected to 2.8Å with an overall Rmerge of 3.9%. Self-rotation Patterson searches were computed in order to identify the 2-fold of the homodimer as well as other possible non-crystallographic symmetry elements. Preliminary cross-rotation searches with a GM-CSF model2 using the above 2-fold in a locked rotation function3 has yielded a possible solution for molecular replacement which we are investigating along with other options for preliminary phasing.


1 Martin FH, et al., (1990), Cell, 63:203.

2 Diederichs K, Boone T & Karplus PA (1991), Science, 254:1779.

3 Tong L & Rossmann M, (1990), Acta Cryst., A46:783.