Keskiaho, K., Kukkola, L., Page, A. P., Winter, A. D., Vuoristo, J., Sormunen, R., Nissi, R., Riihimaa, P. and Myllyharju, J. (2008) Characterization of a novel Caenorhabditis elegans prolyl 4-hydroxylase with a unique substrate specificity and restricted expression in the pharynx and excretory duct. Journal of Biological Chemistry, 283(16), pp. 10679-10689. (doi: 10.1074/jbc.M800972200)
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Publisher's URL: http://dx.doi.org/10.1074/jbc.M800972200
Abstract
Collagen prolyl 4-hydroxylases (C-P4Hs) have a critical role in collagen synthesis, since 4-hydroxyproline residues are necessary for folding of the triple-helical molecules. Vertebrate C-P4Hs are α<sub>2</sub>β<sub>2</sub> tetramers in which the β subunit is identical to protein-disulfide isomerase (PDI). Three isoforms of the catalytic α subunit, PHY-1, PHY-2, and PHY-3, have been characterized from Caenorhabditis elegans, PHY-1 and PHY-2 being responsible for the hydroxylation of cuticle collagens, whereas PHY-3 is predicted to be involved in collagen synthesis in early embryos. We have characterized transcripts of two additional C. elegans α subunit-like genes, Y43F8B.4 and C14E2.4. Three transcripts were generated from Y43F8B.4, and a polypeptide encoded by one of them, named PHY-4.1, assembled into active (PHY-4.1)<sub>2</sub>/(PDI-2)<sub>2</sub> tetramers and PHY-4.1/PDI-2 dimers when coexpressed with C. elegans PDI-2 in insect cells. The C14E2.4 transcript was found to have a frameshift leading to the absence of codons for two residues critical for P4H catalytic activity. Thus, C. elegans has altogether four functional C-P4H α subunits, PHY-1, PHY-2, PHY-3, and PHY-4.1. The tetramers and dimers containing recombinant PHY-4.1 had a distinct substrate specificity from the other C-P4Hs in that they hydroxylated poly(L-proline) and certain other proline-rich peptides, including ones that are expressed in the pharynx, in addition to collagen-like peptides. These data and the observed restricted expression of the phy-4.1 transcript and PHY-4.1 polypeptide in the pharyngeal gland cells and the excretory duct suggest that in addition to collagens, PHY-4.1 may hydroxylate additional proline-rich proteins in vivo.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Page, Professor Tony and Winter, Dr Alan |
Authors: | Keskiaho, K., Kukkola, L., Page, A. P., Winter, A. D., Vuoristo, J., Sormunen, R., Nissi, R., Riihimaa, P., and Myllyharju, J. |
Subjects: | Q Science > QH Natural history > QH345 Biochemistry |
College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | Journal of Biological Chemistry |
Journal Abbr.: | J Biol Chem. |
Publisher: | American Society for Biochemistry and Molecular Biology, Inc. |
ISSN: | 0021-9258 |
ISSN (Online): | 1083-351X |
Published Online: | 13 February 2008 |
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