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A 'dimmer switch' for genes

t, putting a gold star here and a diamond there. These modifications give the protein different properties."

The "decorations" that were studied were phosphate molecules, which previously had been shown to build up on proteins until a certain number accumulated. The result, according to the study, has been described in the past as a sharp on-off switch of protein activity.

"What we found was that each time we added a phosphate to a particular unstructured region of Ets-1, there was an effect on the protein's ability to bind to a gene. Binding was weakened, but it was a gradual weakening. That isn't typical," Graves says. "Instead of acting like an on-off switch, it behaved the way a dimmer switch does to regulate lighting in a gradual manner."

In studying how this fine-tuning worked, they also discovered that conventional wisdom failed to fully describe how proteins function. It was known that proteins have regions with parts that are fixed in space, with a definite structure, and parts that are randomly positioned in space, like spaghetti strands. It was thought that the structured regions did most of the work, while the unstructured regions served only minor roles, such as tethering parts together.

"Scientists understand how a molecule works in part because we understand the shape or structure," Graves explains. "But what we discovered takes us beyond knowing the structure. Our data were about features that are not fixed in space, but that are flexible and changing."

The team used a nuclear magnetic resonance, or NMR, which allows scientists to observe how the atoms of a molecule behave inside a magnetic field. The Graves team found that unstructured regions of the Ets-1 protein were affecting the structured regions in the work of controlling genes. "In fact," Graves reports, "the region's unstructured nature appears to be an essential requirement." NMR showed that phosphate addition to this unstructured region caused a grad
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Source:Huntsman Cancer Institute/University of Utah Health Sciences Center


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