Abstract:
:Because the insolubility of the scrapie prion protein (PrP(Sc)) has frustrated structural studies by x-ray crystallography or NMR spectroscopy, we used electron crystallography to characterize the structure of two infectious variants of the prion protein. Isomorphous two-dimensional crystals of the N-terminally truncated PrP(Sc) (PrP 27-30) and a miniprion (PrP(Sc)106) were identified by negative stain electron microscopy. Image processing allowed the extraction of limited structural information to 7 A resolution. By comparing projection maps of PrP 27-30 and PrP(Sc)106, we visualized the 36-residue internal deletion of the miniprion and localized the N-linked sugars. The dimensions of the monomer and the locations of the deleted segment and sugars were used as constraints in the construction of models for PrP(Sc). Only models featuring parallel beta-helices as the key element could satisfy the constraints. These low-resolution projection maps and models have implications for understanding prion propagation and the pathogenesis of neurodegeneration.
journal_name
Proc Natl Acad Sci U S Aauthors
Wille H,Michelitsch MD,Guenebaut V,Supattapone S,Serban A,Cohen FE,Agard DA,Prusiner SBdoi
10.1073/pnas.052703499keywords:
subject
Has Abstractpub_date
2002-03-19 00:00:00pages
3563-8issue
6eissn
0027-8424issn
1091-6490pii
052703499journal_volume
99pub_type
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