Crystal structure of the human prion protein reveals a mechanism for oligomerization.
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Knaus KJ, Morillas M, Swietnicki W, Malone M, Surewicz WK, Yee VC
Crystal structure of the human prion protein reveals a mechanism for oligomerization.
Nat Struct Biol. 2001 Sep;8(9):770-4.
- PubMed ID
- 11524679 [ View in PubMed]
- 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.