A new angle on a blood-cell hormone.

People who need a boost in red-blood-cell production--anemic patients or those undergoing chemotherapy, for example--often take doses of the natural hormone erythropoietin (EPO). Now, a team of scientists in California has learned more about how EPO stimulates the creation of those cells.

Acting in the bone marrow, EPO binds simultaneously to two closely spaced molecules on the surface of a blood-precursor cell, thus triggering a cascade of biochemical reactions that transform the precursor cell into a red blood cell.

By looking at the three-dimensional structure of EPO with its bound receptor molecules, the researchers saw that the angle the receptors form is crucial. The receptors normally form a 120 [degrees] angle, says Rashid S. Syed of Amgen in Thousand Oaks, Calif. This alignment best triggers the cell's biochemical cascade, he and his colleagues report in the Oct. 1 Nature.

The three-dimensional structure seems to explain why smaller, synthetic proteins designed to bind to EPO receptors don't produce many red blood cells. These mimics move the receptors into a less efficient, 180 [degrees] angle and twist them slightly. Molecules that can correct both the angle and the twist might be better substitutes for EPO, Syed says.