Researchers Define the Structures of Prion Amyloid Variants
summary written by Raven Hanna
While the normal function of human prion protein (PrP) remains a mystery, the results of abnormal PrP are quite well known. Misfolded PrP (denoted PrPSc) leads to diseases such as Creutzfeldt-Jakob disease, mad cow disease, and scrapie in sheep. In these diseases, the protein acts like an infectious agent, recruiting other PrP to become PrPSc without requiring any involvement from nucleic acids or any other molecules. Many PrPSc molecules can bind together to form amyloid structures, similar to those that contribute to a wide variety of diseases including Alzheimer's and Parkinson's.
A research group led by Prof. Gerald Stubbs from Vanderbilt University used SSRL's Beam Line 4-2 to collect fiber diffraction data from hamster and mouse PrPSc amyloids. Results of their measurements were consistent with a beta-helical structure, which had been previously hypothesized from other methods. They also looked at a recombinant PrPSc amyloid that is less infectious than the wild type. The recombinant amyloid structure formed stacked beta-sheets, quite different from the natural amyloid structure. Yet they found that a recombinant PrPSc amyloid isolated from an in vivo system formed the beta-helical structure found in the native amyloid.
The researchers propose that there could be a link between structure and infectivity, but more research must be done to find the basis of the connection. This work was published in the October 6 issue of the Proceedings of the National Academy of Sciences.
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Holger Wille, Wen Bian, Michele McDonald, Amy Kendall, David W. Colby, Lillian Bloch, Julian Ollesch, Alexander L. Borovinskiy, Fred E. Cohen, Stanley B. Prusiner, and Gerald Stubbs (2009) Natural and synthetic prion structure from X-ray fiber diffraction. Proc. Natl. Acad. Sci. USA 106, 16990-95.
