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St. Jude shows how disorderliness in some proteins lets them interact with a diversity of molecules

Investigators at St. Jude Children's Research Hospital have demonstrated for the first time that--contrary to the long-held belief among scientists that proteins must maintain a rigid structure in order to perform an assigned task--many proteins actually exploit disorderliness in their structure to perform a variety of different jobs. The findings of this research appear in the current, online issue of Nature Structural and Molecular Biology.

The St. Jude finding explains how many of the body's proteins can adapt their structures to the needs of the moment, binding to different molecules depending on the job at hand.

"The potential importance of disorder in the function of some proteins has been discussed by researchers for several years," said Richard W. Kriwacki, PhD, associate member of the St. Jude Department of Structural Biology and senior author of the report. "But until now no one had actually demonstrated how such flexibility allows a protein to interact with different molecules. We've taken a big step in understanding the subtle details of a critical biochemical process in the life of the cell."

Previously, other researchers suggested that 30 to 40 percent of the body's proteins do not rely on a rigid structure to interact with target molecules. In the current study, the St. Jude team verified that idea by showing how a protein called p27 uses two flexible arms to help it bind to a protein complex called Cdk2-cyclin A. This interaction is important because Cdk2-cyclin A is one of the so-called "master timekeepers" of cell division. These timekeepers trigger sequential events leading to the production of new daughter cells. By binding to Cdk2-cyclin A and blocking its activity, p27 disrupts this sequence and prevents the cell from dividing. The importance of p27's role in regulating cell division is highlighted by findings showing that loss of p27 function is a key contributing factor in several types of cancer.

The researchers demonst
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
19-Mar-2004


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