We are using X-ray crystallography to characterize the hematopoietic receptor superfamily, and to investigate receptor-ligand interactions and receptor activation on a structural level. Previously, we have determined the structures of three of its members, the first two in complex with hGH: growth hormone receptor (in 1991), prolactin receptor (in 1993-94) and tissue factor (in 1994). Synchrotron data was required in the last two cases (collected at SSRL and CHESS, respectively). The tissue factor structure was originally determined at a resolution of 2.4 _, then data collected at CHESS was used to refine the structure to 1.69 _, making this the highest resolution structure of a cytokine receptor to date. We have now begun to extend our study to the family of tyrosine kinase growth factor receptors, and have recently collected 2 _ data sets for two ligands, vascular endothelial growth factor (VEGF) and glial-cell derived growth factor, as well as for the neurotrophin-5 binding domain of the TrkB receptor. We have solved the VEGF structure at 2.5 _ resolution using data collected in-house, and now are refining it at 1.9 _ using our CHESS data set. Heavy atom derivatives will be required to solve the other structures.
Showing the most recent 10 out of 375 publications
