When cancer cells proliferate, they appear to need the help of a protein called survivin: The protein is abundant in cancer cells but almost absent from normal cells. This dependence makes survivin a particularly inviting target for new anticancer drugs, but how to attack survivin has been a bit of a mystery. Now researchers report that survivin unexpectedly joins together in pairs--a finding that could suggest new opportunities for drug design.
Survivin belongs to a class of proteins that prevent cells from self-destructing, a process known as apoptosis. These proteins inhibit enzymes called caspases that send a cell spiraling into suicide. Yet no one had seen survivin interacting with caspases. And other evidence suggested that survivin serves a different purpose, helping cells pull apart properly after they divide.
To figure out what survivin is up to, structural biologist Joseph Noel of the Salk Institute for Biological Studies in La Jolla, California, and colleagues took the first good look at its three-dimensional structure. They shined x-rays through crystals of survivin and measured how the x-rays were bent; this allowed them to determine the position of each atom in the protein. The structure suggests that survivin forms an alliance that other apoptosis inhibitors don't form. One part of a survivin molecule unexpectedly hooks up with its counterpart on another survivin molecule, forming a protein pair called a dimer, the researchers report in the July issue of Nature Structural Biology. They speculate that these dimers of survivin might support key cellular structures when the cell divides. If the protein has to be paired up to work, breaking it apart with a small molecule might be one way to fight cancer.
Knowing the structure of survivin "doesn't clear up the controversy" about how it prevents cell suicide, says biochemist Guy Salvesen of the Burnham Institute in La Jolla. But the fact that the protein pairs up is surprising, he says, and "you rarely see a dimerization domain that isn't important." He agrees that the interface between the two proteins would be a good place to focus anticancer drugs.
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