Journal article
The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases
- Abstract:
- Biochemical, structural, and cellular studies reveal Jumonji-C (JmjC) domain-containing 7 (JMJD7) as a 2-oxoglutarate (2OG)-dependent oxygenase catalyzing a previously unreported type of post translational modification, (3S)-lysyl hydroxylation. Crystallographic analyses reveal JMJD7 as more closely related to the JmjC hydroxylases rather than the JmjC demethylases. Biophysical and mutation studies show that JMJD7 has a unique dimerization mode, with interactions between monomers involving both N- and C-terminal regions and disulfide bond formation. A proteomic approach identifies two related members of the Translation Factor (TRAFAC) family of GTPases, Developmentally Regulated GTP Binding Proteins 1 and 2 (DRG1/2), as activity-dependent JMJD7 interactors. Mass spectrometric analyses demonstrate that JMJD7 catalyzes Fe(II)- and 2OG dependent hydroxylation of a highly-conserved lysine residue in DRG1/2; amino acid analyses reveal JMJD7 catalyzes (3S)-lysyl hydroxylation. The functional assignment of JMJD7 will enable future studies to define the role of DRG hydroxylation in cell growth and disease.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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Access Document
- Files:
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(Preview, Accepted manuscript, pdf, 1.4MB, Terms of use)
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- Publisher copy:
- 10.1038/s41589-018-0071-y
Authors
Funding
+ Biotechnology and Biological Sciences Research Council
More from this funder
Funding agency for:
Schofield, CJ
Grant:
106244/Z/14/Z
+ Kellogg College, Oxford
More from this funder
Funding agency for:
Abboud, MI
Grant:
Junior Research Fellowship
Bibliographic Details
- Publisher:
- Springer Nature
- Journal:
- Nature Chemical Biology More from this journal
- Volume:
- 14
- Pages:
- 688–695
- Publication date:
- 2018-06-18
- Acceptance date:
- 2018-04-09
- DOI:
- EISSN:
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1552-4469
- ISSN:
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1552-4450
Item Description
- Pubs id:
-
pubs:835039
- UUID:
-
uuid:62b9cef7-9260-4913-8914-346bd0d166bf
- Local pid:
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pubs:835039
- Source identifiers:
-
835039
- Deposit date:
-
2018-04-11
Terms of use
- Copyright holder:
- Markolovic et al
- Copyright date:
- 2018
- Notes:
-
This is the accepted manuscript version of the article. The final version is available online from Springer Nature at: https://doi.org/10.1038/s41589-018-0071-y
Note: an erratum exists for this article, originally published and available at: https://doi.org/10.1038/s41589-018-0104-6
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