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PLATE 2-1 Depiction of the three-dimensional structure of the intact human prion protein, PrP (23-230~. The a-helices are orange, the p-sheets blue. The segments with nonregular secondary structure within the C-te'lllinal domain are yellow. Yellow dots represent the flexibly disordered tail composed of residues 23-121. Reprinted from Zahn et al. (2000) with permission from Proceedings of the National Academy of the United States (2000~. Copyright 2000, Proceedings of the National Academy of the United States.
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b. ... is, ~~.~ Phi Ad_ , .~ PLATE 2-2 Hypothetical models of PrP 27-30, the pro/ease-resistant segment of PrPSc. (a) Three PrP 27-30 polypeptide models scaled and positioned to reflect the presumed structure of the crystal in the background. Each polypeptide has three p- sheet regions (blue) and two a-helices (red). The background is an electron micrograph of a two-dimensional crystal of PrP 27-30 after image processing. (b) A side view of the hypothesized structure of a short segment of a scrapie-associated fibril. Multiple sets of PrP 27-30 polypeptide trimers, viewed from above in (a), are stacked here to form part of a rod-shaped fibril. SOURCES: electron micrograph: H. Wille, Institute for Neurodegenerative Diseases, University of California, San Francisco, July 2003; models: C. Govaerts, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, July 2003.
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Normal sCJ :) vCUD PLATE 4-1 The results of hematoxylin and eosin (HOE) staining (top row) and of immunohistochemical staining (IHC) of PrP (bottom row) are visible in microphotography of human brain tissue from a normal brain, the brain of a patient with sCID, and the brain of a patient with vCID. Top row: The white spaces in sCTD and vCID tissue are vacuoles, a sign of neurodegeneration described as spongiform. In sCTD, the vacuoles are minute and evenly distributed; by contrast, in vCID, they are relatively large and mainly clustered around plaques in formations commonly called florid plaques or daisy plaques the hallmark of vCID. Bottom row: The IHC technique used on these tissues stains PrP brown and removes PrPC, hence the absence of staining in normal tissue. The fine, ubiquitous brown stain in sCID tissue indicates a fairly even distribution of PrPSC, whereas the spotty, intense brown stains in vCJD tissue reflect an uneven distribution of the protein, whichhas accumulated in plaques. SOURCE: I. Ironside, National CID Surveillance Center, Edinburgh, and P. Gambetti, National Prion Disease Pathology Surveillance Center, Cleveland, Ohio, September 2003.
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