| Title: |
The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases |
| Authors: |
Markolovic, S; Zhuang, Q; Wilkins, SE; Eaton, CD; Abboud, MI; Katz, MJ; McNeil, HE; Leśniak, R; Hall, C; Struwe, WB; Konietzny, R; Davis, S; Yang, M; Ge, W; Benesch, JLP; Kessler, BM; Ratcliffe, PJ; Cockman, ME; Fischer, R; Wappner, P; Chowdhury, R; Coleman, M; Schofield, CJ |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2018 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| DOI: |
10.1038/s41589-018-0071-y |
| Availability: |
https://doi.org/10.1038/s41589-018-0071-y; https://ora.ox.ac.uk/objects/uuid:62b9cef7-9260-4913-8914-346bd0d166bf |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.E45ADB4B |
| Database: |
BASE |