Yoshihiro Ishikawa, Yuki Taga, Keith Zientek, Nobuyo Mizuno, Antti M. Salo, Olesya Semenova, Sara F. Tufa, Douglas R. Keene, Paul Holden, Kazunori Mizuno, Douglas B. Gould, Johanna Myllyharju, Hans Peter Bächinger, Type I and type V procollagen triple helix uses different subsets of the molecular ensemble for lysine posttranslational modifications in the rER, Journal of Biological Chemistry, Volume 296, 2021, 100453, ISSN 0021-9258, https://doi.org/10.1016/j.jbc.2021.100453
Type I and type V procollagen triple helix uses different subsets of the molecular ensemble for lysine posttranslational modifications in the rER
|Author:||Ishikawa, Yoshihiro1,2,3; Taga, Yuki4; Zientek, Keith2;|
1Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, Oregon, USA
2Research Department, Shriners Hospital for Children, Portland, Oregon, USA
3Department of Ophthalmology, University of California San Francisco, School of Medicine, San Francisco, California, USA
4Nippi Research Institute of Biomatrix, Ibaraki, Japan
5Oulu Center for Cell-Matrix Research, Biocenter Oulu and Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
6Department of Anatomy, University of California, San Francisco, School of Medicine, San Francisco, California USA
|Online Access:||PDF Full Text (PDF, 4.5 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe2021060935921
American Society for Biochemistry and Molecular Biology,
|Publish Date:|| 2021-06-09
Collagen is the most abundant protein in humans. It has a characteristic triple-helix structure and is heavily posttranslationally modified. The complex biosynthesis of collagen involves processing by many enzymes and chaperones in the rough endoplasmic reticulum. Lysyl hydroxylase 1 (LH1) is required to hydroxylate lysine for cross-linking and carbohydrate attachment within collagen triple helical sequences. Additionally, a recent study of prolyl 3-hydroxylase 3 (P3H3) demonstrated that this enzyme may be critical for LH1 activity; however, the details surrounding its involvement remain unclear. If P3H3 is an LH1 chaperone that is critical for LH1 activity, P3H3 and LH1 null mice should display a similar deficiency in lysyl hydroxylation. To test this hypothesis, we compared the amount and location of hydroxylysine in the triple helical domains of type V and I collagen from P3H3 null, LH1 null, and wild-type mice. The amount of hydroxylysine in type V collagen was reduced in P3H3 null mice, but surprisingly type V collagen from LH1 null mice contained as much hydroxylysine as type V collagen from wild-type mice. In type I collagen, our results indicate that LH1 plays a global enzymatic role in lysyl hydroxylation. P3H3 is also involved in lysyl hydroxylation, particularly at cross-link formation sites, but is not required for all lysyl hydroxylation sites. In summary, our study suggests that LH1 and P3H3 likely have two distinct mechanisms to recognize different collagen types and to distinguish cross-link formation sites from other sites in type I collagen.
Journal of biological chemistry
|Type of Publication:||
A1 Journal article – refereed
|Field of Science:||
1182 Biochemistry, cell and molecular biology
This study was supported by grants from Shriners Hospital for Children (85100 and 85500 to H. P. B.), the Academy of Finland Project Grant 296498 and Center of Excellence 2012–2017 Grant 251314 (J. M.), the S. Jusélius Foundation (J. M.), the Jane and Aatos Erkko Foundation (J. M.) and National Institutes of Neurological Disease and Stroke (R01NS096173 to D. B. G.).
|Academy of Finland Grant Number:||
296498 (Academy of Finland Funding decision)
© 2021 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).