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 a Xaa-Pro-Gly consensus sequence, it may act as a substrate for the collagen modifying enzyme prolyl 4-hydroxylase. Direct
evidence for this modifi-cation 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.
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 a Xaa-Pro-Gly consensus sequence, it may act as a substrate for the collagen modifying enzyme prolyl 4-hydroxylase. Direct
evidence for this modifi-cation 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.
Original language | English |
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Pages (from-to) | 5324-5331 |
Journal | EMBO Journal |
Volume | 19 |
Issue number | 20 |
Publication status | Published - 2000 |
Keywords / Materials (for Non-textual outputs)
- 4-hydroxyproline
- polyproline II helix
- post-translational modification
- prion protein
- prolyl 4-hydroxylase