title: Structural studies of truncated forms of the prion protein PrP.
abstract: Prions are proteins that adopt self-propagating aberrant folds. The self-propagating properties of prions are a direct consequence of their distinct structures, making the understanding of these structures and their biophysical interactions fundamental to understanding prions and their related diseases. The insolubility and inherent disorder of prions have made their structures difficult to study, particularly in the case of the infectious form of the mammalian prion protein PrP. Many investigators have therefore preferred to work with peptide fragments of PrP, suggesting that these peptides might serve as structural and functional models for biologically active prions. We have used x-ray fiber diffraction to compare a series of different-sized fragments of PrP, to determine the structural commonalities among the fragments and the biologically active, self-propagating prions. Although all of the peptides studied adopted amyloid conformations, only the larger fragments demonstrated a degree of structural complexity approaching that of PrP. Even these larger fragments did not adopt the prion structure itself with detailed fidelity, and in some cases their structures were radically different from that of pathogenic PrP(Sc).
authors: Department of Biological Sciences and Center for Structural Biology, Vanderbilt University, Nashville, Tennessee.
authors: William
authors: W
authors: Wan
authors: Institute for Neurodegenerative Diseases and Department of Neurology, University of California, San Francisco, San Francisco, California.
authors: Holger
authors: H
authors: Wille
authors: Institute for Neurodegenerative Diseases and Department of Neurology, University of California, San Francisco, San Francisco, California.
authors: Jan
authors: J
authors: Stöhr
authors: Department of Biological Sciences and Center for Structural Biology, Vanderbilt University, Nashville, Tennessee.
authors: Amy
authors: A
authors: Kendall
authors: Department of Biological Sciences and Center for Structural Biology, Vanderbilt University, Nashville, Tennessee.
authors: Wen
authors: W
authors: Bian
authors: Department of Biological Sciences and Center for Structural Biology, Vanderbilt University, Nashville, Tennessee.
authors: Michele
authors: M
authors: McDonald
authors: Department of Biological Sciences and Center for Structural Biology, Vanderbilt University, Nashville, Tennessee.
authors: Sarah
authors: S
authors: Tiggelaar
authors: Institute for Neurodegenerative Diseases and Department of Neurology, University of California, San Francisco, San Francisco, California.
authors: Joel C
authors: JC
authors: Watts
authors: Institute for Neurodegenerative Diseases and Department of Neurology, University of California, San Francisco, San Francisco, California.
authors: Stanley B
authors: SB
authors: Prusiner
authors: Department of Biological Sciences and Center for Structural Biology, Vanderbilt University, Nashville, Tennessee. Electronic address: gerald.stubbs@vanderbilt.edu.
authors: Gerald
authors: G
authors: Stubbs
mesh_terms: D000682:Amyloid / Q000737:chemistry; D000818:Animals; D001921:Brain / Q000378:metabolism; D004926:Escherichia coli; D058851:GPI-Linked Proteins / Q000737:chemistry; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000737:chemistry; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D000682:Amyloid; D058851:GPI-Linked Proteins; D009419:Nerve Tissue Proteins; D011328:Prions; D011994:Recombinant Proteins; C478971:SPRN protein, human; C523856:Sprn protein, mouse