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Trembling hands and molecular handshakes
Date:10/23/2009

ilable for its normal cellular function.

Dr. Niessing's team reports in the online Early Edition of the journal Proceedings of the National Academy of Sciences USA (PNAS) that the Pur-alpha protein itself consists of three copies of a structural unit called the PUR repeat. "The crystal structure of Pur-alpha will make it possible to understand the protein's function in detail, and this could contribute to the development of a therapy for FXTAS", says Dierk Niessing, who leads a junior research group that is jointly funded by the Helmholtz Zentrum Mnchen, the Helmholtz Association and LMU's Gene Center. "With the treatment options we have at the moment, we can only alleviate the symptoms but cannot attack the real cause of the disease."

"A PUR repeat looks like a hand: four so-called beta-strands, corresponding to four fingers, form a beta-sheet, and an adjacent alpha-helix resembles a thumb", explains Almut Graebsch, the first author from Niessing's group. Pairs of PUR repeats bind to each other in a particular configuration that is reminiscent of a handshake, forming a functional unit. In addition to X-ray diffraction, the researchers have used a technique called small angle X-ray scattering, which revealed that the Pur-alpha protein forms dimers two molecules of the protein bind stably to one another. This probably occurs when PUR repeats in separate molecules interact, in a similar way to the repeats within a molecule, to form the handshake structure.

Experiments in animals have shown that the symptoms of FXTAS disappear if extra Pur-alpha is supplied. "Perhaps the condition can be cured if one can find a way of stopping Pur-alpha from binding to long stretches of CGG in mRNA", says Niessing. By mutating the protein, his group has already obtained clues to how Pur-alpha binds to the CGG repeats. The next step is to find out precisely how Pur-alpha binds to RNA. This in turn could suggest ways of preventing the interactions that cause t
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Contact: Dr. Dierk Niessing
niessing@lmb.uni-muenchen.de
49-892-180-76962
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

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