title: Crystal structure of the human prion protein reveals a mechanism for oligomerization.
abstract: The pathogenesis of transmissible encephalopathies is associated with the conversion of the cellular prion protein, PrP(C), into a conformationally altered oligomeric form, PrP(Sc). Here we report the crystal structure of the human prion protein in dimer form at 2 A resolution. The dimer results from the three-dimensional swapping of the C-terminal helix 3 and rearrangement of the disulfide bond. An interchain two-stranded antiparallel beta-sheet is formed at the dimer interface by residues that are located in helix 2 in the monomeric NMR structures. Familial prion disease mutations map to the regions directly involved in helix swapping. This crystal structure suggests that oligomerization through 3D domain-swapping may constitute an important step on the pathway of the PrP(C) --> PrP(Sc) conversion.
authors.affiliation: Department of Molecular Cardiology and Center for Structural Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue NB20, Cleveland, Ohio 44195, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Knaus
authors.forename: M
authors.initials: M
authors.lastname: Morillas
authors.forename: W
authors.initials: W
authors.lastname: Swietnicki
authors.forename: M
authors.initials: M
authors.lastname: Malone
authors.forename: W K
authors.initials: WK
authors.lastname: Surewicz
authors.forename: V C
authors.initials: VC
authors.lastname: Yee
mesh_terms: D018360:Crystallography, X-Ray; D019281:Dimerization; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D011328:Prions / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D004220:Disulfides; D011328:Prions