1FO7

HUMAN PRION PROTEIN MUTANT E200K FRAGMENT 90-231

Summary for 1FO7

• Entry DOI: 10.2210/pdb1fo7/pdb
• Related: 1FKC
• NMR Information: BMRB: 4641
• Descriptor: PRION PROTEIN (1 entity in total)
• Functional Keywords: creutzfeldt-jakob disease, prion, aggregation, membrane protein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Lipid-anchor, GPI-anchor . Isoform 2: Cytoplasm : P04156
• Total number of polymer chains: 1
• Total formula weight: 16169.06

Authors

Zhang, Y.,Swietnicki, W.,Zagorski, M.G.,Surewicz, W.K.,Soennichsen, F.D. (deposition date: 2000-08-25, release date: 2000-09-21, Last modification date: 2024-10-09)

Primary citation

Zhang, Y.,Swietnicki, W.,Zagorski, M.G.,Surewicz, W.K.,Sonnichsen, F.D.
Solution structure of the E200K variant of human prion protein. Implications for the mechanism of pathogenesis in familial prion diseases.
J.Biol.Chem., 275:33650-33654, 2000

PubMed Abstract: Prion propagation in transmissible spongiform encephalopathies involves the conversion of cellular prion protein, PrP(C), into a pathogenic conformer, PrP(Sc). Hereditary forms of the disease are linked to specific mutations in the gene coding for the prion protein. To gain insight into the molecular basis of these disorders, the solution structure of the familial Creutzfeldt-Jakob disease-related E200K variant of human prion protein was determined by multi-dimensional nuclear magnetic resonance spectroscopy. Remarkably, apart from minor differences in flexible regions, the backbone tertiary structure of the E200K variant is nearly identical to that reported for the wild-type human prion protein. The only major consequence of the mutation is the perturbation of surface electrostatic potential. The present structural data strongly suggest that protein surface defects leading to abnormalities in the interaction of prion protein with auxiliary proteins/chaperones or cellular membranes should be considered key determinants of a spontaneous PrP(C) --> PrP(Sc) conversion in the E200K form of hereditary prion disease.

PubMed: 10954699
DOI: 10.1074/jbc.C000483200

Experimental method

SOLUTION NMR