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Proteins' subtle 'backrub' motion could have important implications

Biochemists have detected a surprising, subtle new gyration that protein molecules undergo in the intricate, squirming dance that influences their activity in the cell. The researchers have also created a realistic geometrical model of the twisting "backrub" motion that could help scientists understand the basics of protein function and design proteins for medical use.

Also, they said, the backrub motion could have implications for understanding how proteins can accommodate locally to some mutations that occur during evolution, without altering their global structure or function.

Understanding the subtleties of protein motion is important because the molecules are central to the machinery of life. For example, protein enzymes catalyze the myriad of chemical reactions that underlie all cell functions. Thus, biologists seek not only to understand the complexities of protein dynamics, but to design and construct manmade proteins as medicines to treat a wide array of diseases.

The Duke University Medical Center biochemists, led by Professors Jane and David Richardson, published their findings in the February 2006 issue of the journal Structure. Lead author on the paper was graduate student Ian Davis, and the other co-author was Bryan Arendall. The research was supported by the National Institutes of Health and a Howard Hughes Medical Institute predoctoral fellowship to Davis.

Proteins comprise strings of amino acids whose links form a "backbone." Each kind of amino acid sprouts a characteristic molecular "side chain," and together the backbone and side chains determine a protein's structure and function.

The Duke researchers suspected the presence of backrub motions for other reasons, but their reality could be conclusively shown only by studying proteins frozen in crystalline form for structural analysis by x-ray crystallography. In this widely used technique, x-rays are directed through crystals of a protein, and the pattern of
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Contact: Dennis Meredith
dennis.meredith@duke.edu
919-681-8054
Duke University Medical Center
7-Feb-2006


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