Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 370772
Title Methionine Sulfoxides on PrPSc: A Prion-Specific Covalent Signature
Author(s) Canello, T.; Engelstein, R.; Moshel, O.; Xanthopoulos, K.; Langeveld, J.P.M.; Sklaviadis, T.; Gasset, M.; Gabizon, R.
Source Biochemistry 47 (2008)34. - ISSN 0006-2960 - p. 8866 - 8873.
DOI https://doi.org/10.1021/bi800801f
Department(s) CVI - Division Virology
Publication type Refereed Article in a scientific journal
Publication year 2008
Keyword(s) in-vitro - oxidative stress - protein - scrapie - disease - glycosylation - purification - proteasome - conversion - complexes
Abstract Prion diseases are fatal neurodegenerative disorders believed to be transmitted by PrPSc, an aberrant form of the membrane protein PrPC. In the absence of an established form-specific covalent difference, the infectious properties of PrPSc were uniquely ascribed to the self-perpetuation properties of its aberrant fold. Previous sequencing of the PrP chain isolated from PrP(27¿30) showed the oxidation of some methionine residues; however, at that time, these findings were ascribed to experimental limitations. Using the unique recognition properties of ¿PrP mAb IPC2, protein chemistry, and state of the art mass spectrometry, we now show that while a large fraction of the methionine residues in brain PrPSc are present as methionine sulfoxides this modification could not be found on brain PrPC as well as on its recombinant models. In particular, the pattern of oxidation of M213 with respect to the glycosylation at N181 of PrPSc differs both within and between species, adding another diversity factor to the structure of PrPSc molecules. Our results pave the way for the production of prion-specific reagents in the form of antibodies against oxidized PrP chains which can serve in the development of both diagnostic and therapeutic strategies. In addition, we hypothesize that the accumulation of PrPSc and thereafter the pathogenesis of prion disease may result from the poor degradation of oxidized aberrantly folded PrP.
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