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

Gill, Andrew C., Ritchie, Mark A., Hunt, Lawrence G., Steane, Sarah E., Davies, Kenneth G., Bocking, Sharon P., Rhie, Alexandre G. O., Bennett, Alan D. and Hope, James (2000) Post-translational hydroxylation at the N-terminus of the prion protein reveals presence of PPII structure in vivo. EMBO Journal, 19 (20). pp. 5324-5331. ISSN 0261-4189

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Abstract

The transmissible spongiform encephalopathies are characterized by conversion of a host protein, PrP(C) (cellular prion protein), to a protease-resistant isoform, PrP(Sc) (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 PrP(Sc) 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.

Item Type:	Article
Uncontrolled Keywords:	4-hydroxyproline,polyproline ii helix,post-translational modifications,prion protein,prolyl 4-hydroxylase,neuroscience(all),molecular biology,biochemistry, genetics and molecular biology(all),immunology and microbiology(all) ,/dk/atira/pure/subjectarea/asjc/2800
Faculty \ School:	Faculty of Science > School of Biological Sciences
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	05 Dec 2025 13:30
Last Modified:	10 Dec 2025 14:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/101286
DOI:	10.1093/emboj/19.20.5324

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