Recently, in the April 30, 1999 issue of the journal Science, Drs. Culotta and O'Halloran reported that this second chaperone protein directly supplies a molecule of copper to SOD and showed how the chaperone is a necessary ingredient for the free radical-destroying protein's activity.
"No one thought SOD would need a chaperone," said Dr. Culotta. A long-standing paradox, she noted, was that although in a test tube SOD soaks up copper molecules like a sponge, "[SOD] can't find copper inside a living cell." She and her collaborators now recognize that this is because the potentially dangerous metal is so well hidden, bound up by several protective proteins.
"Only vanishingly small amounts of free metal are normally available in cells, and elevated levels may only be present in disease," said Dr. Peter Preusch, a biochemist at NIGMS. He described the new work as being "of profound significance."
According to Dr. O'Halloran, the recent findings render the copper chaperone a "suspect in the mystery of Lou Gehrig's disease--but suspects are just that. This may be a case of guilt by association."
In a continuing quest to reveal the secrets of how copper traffics throughout a
cell, recently Dr. O'Halloran teamed up with a Northwestern colleague, Dr. Amy
Rosenzweig, to unravel the structure, or three-dimensional shape, of the copper
chaperone protein. Dr. Rosenzweig is well-versed in determining the structures
of proteins, using a technique called X-ray crystallography. In this technique,
scientists bombard a tiny crystal of protein with high-energy X-rays, then piece
together the protein's shape by tracing the directions in which the energy is
scattered. According to Dr. Rosenzweig, knowing what a protein looks like can
say a lot about how it works.
Contact: Alison Davis
NIH/National Institute of General Medical Sciences