Biochemical and physical properties of the prion protein from two strains of the transmissible mink encephalopathy agent. (original) (raw)
- Journal List
- J Virol
- v.66(4); 1992 Apr
- PMC289000
J Virol. 1992 Apr; 66(4): 2096–2101.
Department of Veterinary Science, University of Wisconsin-Madison 53706.
Abstract
Transmissible mink encephalopathy (TME) has been transmitted to Syrian golden hamsters, and two strains of the causative agent, HYPER (HY) and DROWSY (DY), have been identified that have different biological properties. During scrapie, a TME-like disease, an endogenous cellular protein, the prion protein (PrPC), is modified (to PrPSc) and accumulates in the brain. PrPSc is partially resistant to proteases and is claimed to be an essential component of the infectious agent. Purification and analysis of PrP from hamsters infected with the HY and DY TME agent strains revealed differences in properties of PrPTME sedimentation in N-lauroylsarcosine, sensitivity to digestion with proteinase K, and migration in polyacrylamide gels. PrPC and HY PrPTME can be distinguished on the basis of their relative solubilities in detergent and protease sensitivities. PrPTME from DY-infected brain tissue shared solubility characteristics of PrP from both uninfected and HY-infected tissue. Limited protease digestion of PrPTME revealed strain-specific migration patterns upon polyacrylamide gel electrophoresis. Prolonged proteinase K treatment or N-linked deglycosylation of PrPTME did not eliminate such differences but demonstrated the PrPTME from DY-infected brain was more sensitive to protease digestion than HY PrPTME. Antigenic mapping of PrPTME with antibodies raised against synthetic peptides revealed strain-specific differences in immunoreactivity in a region of the amino-terminal end of PrPTME containing amino acid residues 89 to 103. These findings indicate that PrPTME from the two agent strains, although originating from the same host, differ in composition, conformation, or both. We conclude that PrPTME from the HY and DY strains undergo different posttranslational modifications that could explain differences in the biochemical properties of PrPTME from the two sources. Whether these strain-specific posttranslational events are directly responsible for the distinct biological properties of the HY and DY agent strains remains to be determined.
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- Barry RA, McKinley MP, Bendheim PE, Lewis GK, DeArmond SJ, Prusiner SB. Antibodies to the scrapie protein decorate prion rods. J Immunol. 1985 Jul;135(1):603–613. [PubMed] [Google Scholar]
- Bellinger-Kawahara CG, Kempner E, Groth D, Gabizon R, Prusiner SB. Scrapie prion liposomes and rods exhibit target sizes of 55,000 Da. Virology. 1988 Jun;164(2):537–541. [PubMed] [Google Scholar]
- Bendheim PE, Barry RA, DeArmond SJ, Stites DP, Prusiner SB. Antibodies to a scrapie prion protein. Nature. 1984 Aug 2;310(5976):418–421. [PubMed] [Google Scholar]
- Blake MS, Johnston KH, Russell-Jones GJ, Gotschlich EC. A rapid, sensitive method for detection of alkaline phosphatase-conjugated anti-antibody on Western blots. Anal Biochem. 1984 Jan;136(1):175–179. [PubMed] [Google Scholar]
- Bockman JM, Kingsbury DT. Immunological analysis of host and agent effects on Creutzfeldt-Jakob disease and scrapie prion proteins. J Virol. 1988 Sep;62(9):3120–3127. [PMC free article] [PubMed] [Google Scholar]
- Bode L, Pocchiari M, Gelderblom H, Diringer H. Characterization of antisera against scrapie-associated fibrils (SAF) from affected hamster and cross-reactivity with SAF from scrapie-affected mice and from patients with Creutzfeldt-Jakob disease. J Gen Virol. 1985 Nov;66(Pt 11):2471–2478. [PubMed] [Google Scholar]
- Bolton DC, Bendheim PE. A modified host protein model of scrapie. Ciba Found Symp. 1988;135:164–181. [PubMed] [Google Scholar]
- Bolton DC, McKinley MP, Prusiner SB. Identification of a protein that purifies with the scrapie prion. Science. 1982 Dec 24;218(4579):1309–1311. [PubMed] [Google Scholar]
- Bruce ME, Dickinson AG. Biological evidence that scrapie agent has an independent genome. J Gen Virol. 1987 Jan;68(Pt 1):79–89. [PubMed] [Google Scholar]
- Carlson GA, Westaway D, DeArmond SJ, Peterson-Torchia M, Prusiner SB. Primary structure of prion protein may modify scrapie isolate properties. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7475–7479. [PMC free article] [PubMed] [Google Scholar]
- Caughey B, Raymond GJ, Ernst D, Race RE. N-terminal truncation of the scrapie-associated form of PrP by lysosomal protease(s): implications regarding the site of conversion of PrP to the protease-resistant state. J Virol. 1991 Dec;65(12):6597–6603. [PMC free article] [PubMed] [Google Scholar]
- DeArmond SJ, McKinley MP, Barry RA, Braunfeld MB, McColloch JR, Prusiner SB. Identification of prion amyloid filaments in scrapie-infected brain. Cell. 1985 May;41(1):221–235. [PubMed] [Google Scholar]
- Griffith JS. Self-replication and scrapie. Nature. 1967 Sep 2;215(5105):1043–1044. [PubMed] [Google Scholar]
- Haraguchi T, Fisher S, Olofsson S, Endo T, Groth D, Tarentino A, Borchelt DR, Teplow D, Hood L, Burlingame A, et al. Asparagine-linked glycosylation of the scrapie and cellular prion proteins. Arch Biochem Biophys. 1989 Oct;274(1):1–13. [PubMed] [Google Scholar]
- Hilmert H, Diringer H. A rapid and efficient method to enrich SAF-protein from scrapie brains of hamsters. Biosci Rep. 1984 Feb;4(2):165–170. [PubMed] [Google Scholar]
- Hope J, Morton LJ, Farquhar CF, Multhaup G, Beyreuther K, Kimberlin RH. The major polypeptide of scrapie-associated fibrils (SAF) has the same size, charge distribution and N-terminal protein sequence as predicted for the normal brain protein (PrP). EMBO J. 1986 Oct;5(10):2591–2597. [PMC free article] [PubMed] [Google Scholar]
- Hope J, Multhaup G, Reekie LJ, Kimberlin RH, Beyreuther K. Molecular pathology of scrapie-associated fibril protein (PrP) in mouse brain affected by the ME7 strain of scrapie. Eur J Biochem. 1988 Mar 1;172(2):271–277. [PubMed] [Google Scholar]
- Hsiao K, Baker HF, Crow TJ, Poulter M, Owen F, Terwilliger JD, Westaway D, Ott J, Prusiner SB. Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome. Nature. 1989 Mar 23;338(6213):342–345. [PubMed] [Google Scholar]
- Hsiao KK, Scott M, Foster D, Groth DF, DeArmond SJ, Prusiner SB. Spontaneous neurodegeneration in transgenic mice with mutant prion protein. Science. 1990 Dec 14;250(4987):1587–1590. [PubMed] [Google Scholar]
- Kascsak RJ, Rubenstein R, Merz PA, Carp RI, Robakis NK, Wisniewski HM, Diringer H. Immunological comparison of scrapie-associated fibrils isolated from animals infected with four different scrapie strains. J Virol. 1986 Sep;59(3):676–683. [PMC free article] [PubMed] [Google Scholar]
- Kascsak RJ, Rubenstein R, Merz PA, Carp RI, Wisniewski HM, Diringer H. Biochemical differences among scrapie-associated fibrils support the biological diversity of scrapie agents. J Gen Virol. 1985 Aug;66(Pt 8):1715–1722. [PubMed] [Google Scholar]
- Kascsak RJ, Rubenstein R, Merz PA, Tonna-DeMasi M, Fersko R, Carp RI, Wisniewski HM, Diringer H. Mouse polyclonal and monoclonal antibody to scrapie-associated fibril proteins. J Virol. 1987 Dec;61(12):3688–3693. [PMC free article] [PubMed] [Google Scholar]
- Kimberlin RH. Scrapie agent: prions or virinos? Nature. 1982 May 13;297(5862):107–108. [PubMed] [Google Scholar]
- Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed] [Google Scholar]
- Marsh RF, Bessen RA, Lehmann S, Hartsough GR. Epidemiological and experimental studies on a new incident of transmissible mink encephalopathy. J Gen Virol. 1991 Mar;72(Pt 3):589–594. [PubMed] [Google Scholar]
- McKinley MP, Meyer RK, Kenaga L, Rahbar F, Cotter R, Serban A, Prusiner SB. Scrapie prion rod formation in vitro requires both detergent extraction and limited proteolysis. J Virol. 1991 Mar;65(3):1340–1351. [PMC free article] [PubMed] [Google Scholar]
- Merz PA, Somerville RA, Wisniewski HM, Iqbal K. Abnormal fibrils from scrapie-infected brain. Acta Neuropathol. 1981;54(1):63–74. [PubMed] [Google Scholar]
- Meyer RK, McKinley MP, Bowman KA, Braunfeld MB, Barry RA, Prusiner SB. Separation and properties of cellular and scrapie prion proteins. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2310–2314. [PMC free article] [PubMed] [Google Scholar]
- Prusiner SB. Novel proteinaceous infectious particles cause scrapie. Science. 1982 Apr 9;216(4542):136–144. [PubMed] [Google Scholar]
- Prusiner SB, Bolton DC, Groth DF, Bowman KA, Cochran SP, McKinley MP. Further purification and characterization of scrapie prions. Biochemistry. 1982 Dec 21;21(26):6942–6950. [PubMed] [Google Scholar]
- Prusiner SB, Scott M, Foster D, Pan KM, Groth D, Mirenda C, Torchia M, Yang SL, Serban D, Carlson GA, et al. Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell. 1990 Nov 16;63(4):673–686. [PubMed] [Google Scholar]
- Stahl N, Baldwin MA, Burlingame AL, Prusiner SB. Identification of glycoinositol phospholipid linked and truncated forms of the scrapie prion protein. Biochemistry. 1990 Sep 25;29(38):8879–8884. [PubMed] [Google Scholar]
- Stahl N, Borchelt DR, Hsiao K, Prusiner SB. Scrapie prion protein contains a phosphatidylinositol glycolipid. Cell. 1987 Oct 23;51(2):229–240. [PubMed] [Google Scholar]
- Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. [PMC free article] [PubMed] [Google Scholar]
- Turk E, Teplow DB, Hood LE, Prusiner SB. Purification and properties of the cellular and scrapie hamster prion proteins. Eur J Biochem. 1988 Sep 1;176(1):21–30. [PubMed] [Google Scholar]
- WILSON DR, ANDERSON RD, SMITH W. Studies in scrapie. J Comp Pathol. 1950 Oct;60(4):267–282. [PubMed] [Google Scholar]
- Wray W, Boulikas T, Wray VP, Hancock R. Silver staining of proteins in polyacrylamide gels. Anal Biochem. 1981 Nov 15;118(1):197–203. [PubMed] [Google Scholar]
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