Strain-specific prion-protein conformation determined by metal ions - PubMed (original) (raw)
Strain-specific prion-protein conformation determined by metal ions
J D Wadsworth et al. Nat Cell Biol. 1999 May.
Abstract
In animals infected with a transmissible spongiform encephalopathy, or prion disease, conformational isomers (known as PrPSc proteins) of the wild-type, host-encoded cellular prion protein (PrPc) accumulate. The infectious agents, prions, are composed mainly of these conformational isomers, with distinct prion isolates or strains being associated with different PrPSc conformations and patterns of glycosylation. Here we show that two different human PrPSc types, seen in clinically distinct subtypes of classical Creutzfeldt-Jakob disease, can be interconverted in vitro by altering their metal-ion occupancy. The dependence of PrPSc conformation on the binding of copper and zinc represents a new mechanism for post-translational modification of PrP and for the generation of multiple prion strains, with widespread implications for both the molecular classification and the pathogenesis of prion diseases in humans and animals.
Comment in
- The strain of copper on the brain.
Coles H. Coles H. Nat Cell Biol. 1999 May;1(1):E7. doi: 10.1038/8955. Nat Cell Biol. 1999. PMID: 10559871 No abstract available.
Similar articles
- Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD.
Collinge J, Sidle KC, Meads J, Ironside J, Hill AF. Collinge J, et al. Nature. 1996 Oct 24;383(6602):685-90. doi: 10.1038/383685a0. Nature. 1996. PMID: 8878476 - Insights into Mechanisms of Transmission and Pathogenesis from Transgenic Mouse Models of Prion Diseases.
Moreno JA, Telling GC. Moreno JA, et al. Methods Mol Biol. 2017;1658:219-252. doi: 10.1007/978-1-4939-7244-9_16. Methods Mol Biol. 2017. PMID: 28861793 Free PMC article. Review. - Prion protein glycosylation.
Lawson VA, Collins SJ, Masters CL, Hill AF. Lawson VA, et al. J Neurochem. 2005 May;93(4):793-801. doi: 10.1111/j.1471-4159.2005.03104.x. J Neurochem. 2005. PMID: 15857383 Review. - Prion-induced neuronal damage--the mechanisms of neuronal destruction in the subacute spongiform encephalopathies.
Giese A, Kretzschmar HA. Giese A, et al. Curr Top Microbiol Immunol. 2001;253:203-17. doi: 10.1007/978-3-662-10356-2_10. Curr Top Microbiol Immunol. 2001. PMID: 11417136 Review. - The cellular prion protein: biochemistry, topology, and physiologic functions.
Griffoni C, Toni M, Spisni E, Bianco M, Santi S, Riccio M, Tomasi V. Griffoni C, et al. Cell Biochem Biophys. 2003;38(3):287-304. doi: 10.1385/cbb:38:3:287. Cell Biochem Biophys. 2003. PMID: 12794269 Review.
Cited by
- Molecular pathogenesis of sporadic prion diseases in man.
Safar JG. Safar JG. Prion. 2012 Apr-Jun;6(2):108-15. doi: 10.4161/pri.18666. Epub 2012 Apr 1. Prion. 2012. PMID: 22421210 Free PMC article. Review. - Separation of native prion protein (PrP) glycoforms by copper-binding using immobilized metal affinity chromatography (IMAC).
Müller H, Strom A, Hunsmann G, Stuke AW. Müller H, et al. Biochem J. 2005 May 15;388(Pt 1):371-8. doi: 10.1042/BJ20041291. Biochem J. 2005. PMID: 15658935 Free PMC article. - Microsecond unfolding kinetics of sheep prion protein reveals an intermediate that correlates with susceptibility to classical scrapie.
Chen KC, Xu M, Wedemeyer WJ, Roder H. Chen KC, et al. Biophys J. 2011 Sep 7;101(5):1221-30. doi: 10.1016/j.bpj.2011.07.024. Biophys J. 2011. PMID: 21889460 Free PMC article. - Zinc and Copper Ions Differentially Regulate Prion-Like Phase Separation Dynamics of Pan-Virus Nucleocapsid Biomolecular Condensates.
Monette A, Mouland AJ. Monette A, et al. Viruses. 2020 Oct 18;12(10):1179. doi: 10.3390/v12101179. Viruses. 2020. PMID: 33081049 Free PMC article. - Copper induces increased beta-sheet content in the scrapie-susceptible ovine prion protein PrPVRQ compared with the resistant allelic variant PrPARR.
Wong E, Thackray AM, Bujdoso R. Wong E, et al. Biochem J. 2004 May 15;380(Pt 1):273-82. doi: 10.1042/BJ20031767. Biochem J. 2004. PMID: 14969585 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials