Purified scrapie prions resist inactivation by procedures that hydrolyze, modify, or shear nucleic acids

Bellinger-Kawahara, Carolyn; Diener, T.O.; McKinley, Michael P.; Groth, Darlene; Smith, D. B.; Prusiner, Stanley B.

doi:10.1016/0042-6822(87)90072-9

Cited by 84 publications

(30 citation statements)

References 26 publications

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“…These results, and numerous unsuccessful attempts to detect a scrapiespecific nucleic acid (36)(37)(38)(39)(40), militate against a foreign nucleic acid as an essential component of the "infectious" prion, despite proposals to the contrary (32, [41][42][43] …”

Section: Methodsmentioning

confidence: 99%

Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein.

Hsiao

Groth

Scott

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

259

134

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Section: Methodsmentioning

confidence: 99%

Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein.

Hsiao

Groth

Scott

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

259

134

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“…3 M GdnSCN) that modify the structure of PrP 27-30 also inactivate prion infectivity (25). In contrast, prion infectivity resists inactivation by reagents that disrupt nucleic acid polymers including nucleases, psoralens, and UV irradiation (50,(59)(60)(61)(62)(63). Microsequencing of the N-terminus of PrP 27-30 (54) led to the cloning and sequencing of the PrP gene (38,55 The N-terminus of PrP 27-30 corresponds to approximately codon 90 in the full-length coding sequence (57,64).…”

Section: Biochemical Characterizationmentioning

confidence: 99%

Pathologic Conformations of Prion Proteins

Cohen

Prusiner

1998

Annu. Rev. Biochem.

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497

379

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While many aspects of prion disease biology are unorthodox, perhaps the most fundamental paradox is posed by the coexistence of inherited, sporadic, and infectious forms of these diseases. Sensible molecular mechanisms for prion propagation must explain all three forms of prion diseases in a manner that is compatible with the formidable array of experimental data derived from histopathological, biochemical, biophysical, human genetic, and transgenetic studies. In this review, we explore prion disease pathogenesis initially from the perspective of an autosomal dominant inherited disease. Subsequently, we examine how an intrinsically inherited disease could present in sporadic and infectious forms. Finally, we explore the phenomenologic constraints on models of prion replication with a specific emphasis on biophysical studies of prion protein structures. CONTENTS

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“…But both UV and ionizing radiation inactivation studies as well as physical studies have eliminated the possibility of a large nucleic acid hiding within purified preparations of prions (110)(111)(112). Only oligonucleotides of fewer than 50 bases were found at a concentration of one molecule per ID 50 unit in prion preparations highly enriched for scrapie infectivity (113,114).…”

mentioning

confidence: 99%

“…The inability to inactivate preparations highly enriched for scrapie infectivity by procedures that modify nucleic acids militates against the existence of a scrapie-specific nucleic acid (58,110,111). To explain the findings in terms of a virus, one must argue that PrP Sc or an as-yet-undetected PrP-like protein of viral origin protects the viral genome from inactivation.…”

mentioning

confidence: 99%

Molecular characterization of proteolytic cleavage sites of the Pseudomonas syringae effector AvrRpt2

Chisholm

Dahlbeck

Krishnamurthy

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

137

138

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Prions are unprecedented infectious pathogens that cause a group of invariably fatal neurodegenerative diseases by an entirely novel mechanism. Prion diseases may present as genetic, infectious, or sporadic disorders, all of which involve modification of the prion protein (PrP). Bovine spongiform encephalopathy (BSE), scrapie of sheep, and Creutzfeldt-Jakob disease (CJD) of humans are among the most notable prion diseases. Prions are transmissible particles that are devoid of nucleic acid and seem to be composed exclusively of a modified protein (PrP Sc ). The normal, cellular PrP (PrP C ) is converted into PrP Sc through a posttranslational process during which it acquires a high ␤-sheet content. The species of a particular prion is encoded by the sequence of the chromosomal PrP gene of the mammals in which it last replicated. In contrast to pathogens carrying a nucleic acid genome, prions appear to encipher strain-specific properties in the tertiary structure of PrP Sc . Transgenetic studies argue that PrP Sc acts as a template upon which PrP C is refolded into a nascent PrP Sc molecule through a process facilitated by another protein. Miniprions generated in transgenic mice expressing PrP, in which nearly half of the residues were deleted, exhibit unique biological properties and should facilitate structural studies of PrP Sc . While knowledge about prions has profound implications for studies of the structural plasticity of proteins, investigations of prion diseases suggest that new strategies for the prevention and treatment of these disorders may also find application in the more common degenerative diseases.

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Purified scrapie prions resist inactivation by procedures that hydrolyze, modify, or shear nucleic acids

Cited by 84 publications

References 26 publications

Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein.

Serial transmission in rodents of neurodegeneration from transgenic mice expressing mutant prion protein.

Pathologic Conformations of Prion Proteins

Molecular characterization of proteolytic cleavage sites of the Pseudomonas syringae effector AvrRpt2

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