Interplays between covalent modifications in the endoplasmic reticulum increase conformational diversity in nascent prion protein.

Andrea Orsi, Roberto Sitia

Research output: Contribution to journalArticle

Abstract

Prion protein (PrP), the causative agent of transmissible spongiform encephalopathies, is synthesized in the endoplasmic reticulum (ER) where it undergoes numerous covalent modifications. Here we investigate the interdependence and regulation of PrP oxidative folding, N-glycosylation and GPI addition in diverse ER conditions. Our results show that formation of the single disulphide bond is a pivotal event, essential for PrP transport, and can occur post-translationally. Retarding its formation enhances N-glycosylation and GPI-anchoring. In contrast, lowering ER Ca(2+) concentration inhibits N-glycosylation and GPI-anchoring. These data reveal tight interplays between the different ER covalent modifications, which collectively increase of PrP conformational diversity and may be important for its propagation.

Original languageEnglish
Pages (from-to)236-242
Number of pages7
JournalPrion
Volume1
Issue number4
Publication statusPublished - Oct 2007

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Glycosylation
Endoplasmic Reticulum
Prion Diseases
Protein Folding
Protein Transport
Disulfides
Prion Proteins
Prions

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Infectious Diseases
  • Cellular and Molecular Neuroscience

Cite this

Interplays between covalent modifications in the endoplasmic reticulum increase conformational diversity in nascent prion protein. / Orsi, Andrea; Sitia, Roberto.

In: Prion, Vol. 1, No. 4, 10.2007, p. 236-242.

Research output: Contribution to journalArticle

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