Post-translational hydroxylation at the N-terminus of the prion protein reveals presence of PPII structure in vivo

Gill, Andrew and Ritchie, M. A. and Hunt, L. G. and Steane, S. E. and Davies, K. G. and Bocking, S. P. and Rhie, A. G. O. and Bennett, A. D. and Hope, J. (2000) Post-translational hydroxylation at the N-terminus of the prion protein reveals presence of PPII structure in vivo. The EMBO Journal, 19 (20). pp. 5324-5331. ISSN 0261-4189

Full content URL: http://emboj.embopress.org/content/19/20/5324

Documents
Gill5324.pdf

Request a copy
[img] PDF
Gill5324.pdf - Whole Document
Restricted to Repository staff only

145kB
Item Type:Article
Item Status:Live Archive

Abstract

The transmissible spongiform encephalopathies are characterized by conversion of a host protein, PrPC (cellular prion protein), to a protease-resistant isoform, PrPSc (prion protein scrapie isoform). The importance of the highly flexible, N-terminal region of PrP has recently become more widely appreciated, particularly the biological activities associated with its metal ion-binding domain and its potential to form a poly(L-proline) II (PPII) helix. Circular dichroism spectroscopy of an N-terminal peptide, PrP37-53, showed that the PPII helix is formed in aqueous buffer; as it also contains an Xaa-Pro-Gly consensus sequence, it may act as a substrate for the collagen-modifying enzyme prolyl 4-hydroxylase. Direct evidence for this modification was obtained by mass spectrometry and Edman sequencing in recombinant mouse PrP secreted from stably transfected Chinese hamster ovary cells. Almost complete conversion of proline to 4-hydroxyproline occurs specifically at residue Pro44 of this murine protein; the same hydroxylated residue was detected, at lower levels, in PrPSc from the brains of scrapie-infected mice. Cation binding and/or post-translational hydroxylation of this region of PrP may regulate its role in the physiology and pathobiology of the cell.

Keywords:hydroxyproline, polyproline helix, post translational modification, prion protein, prolyl hydroxylase
Subjects:C Biological Sciences > C760 Biomolecular Science
Divisions:College of Science
ID Code:29578
Deposited On:30 Aug 2018 12:27

Repository Staff Only: item control page