1FKC

HUMAN PRION PROTEIN (MUTANT E200K) FRAGMENT 90-231

1FKC の概要

• エントリーDOI: 10.2210/pdb1fkc/pdb
• 分子名称: PRION PROTEIN (1 entity in total)
• 機能のキーワード: three helix, creutzfeldt-jakob disease, prion, aggregation, membrane protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane; Lipid-anchor, GPI-anchor . Isoform 2: Cytoplasm : P04156
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16169.06

構造登録者

Zhang, Y.,Swietnicki, W.,Zagorski, M.G.,Surewicz, W.K.,Soennichsen, F.D. (登録日: 2000-08-09, 公開日: 2000-09-21, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

SOLUTION NMR