Crystal structure of the human prion protein reveals a mechanism for oligomerization.
Top Cited Papers
- 1 September 2001
- journal article
- Published by Springer Nature in Nature Structural & Molecular Biology
- Vol. 8 (9) , 770-774
- https://doi.org/10.1038/nsb0901-770
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.Keywords
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