The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases
journal contributionposted on 27.08.2020 by Suzana Markolovic, Qinqin Zhuang, Sarah E Wilkins, Charlotte D Eaton, Martine I Abboud, Maximiliano J Katz, Helen E McNeil, Robert K Leśniak, Charlotte Hall, Weston B Struwe, Rebecca Konietzny, Simon Davis, Ming Yang, Wei Ge, Justin LP Benesch, Benedikt M Kessler, Peter J Ratcliffe, Matthew E Cockman, Roman Fischer, Pablo Wappner, Rasheduzzaman Chowdhury, Mathew L Coleman, Christopher J Schofield
Any type of content formally published in an academic journal, usually following a peer-review process.
Biochemical, structural and cellular studies reveal Jumonji-C (JmjC) domain-containing 7 (JMJD7) to be a 2-oxoglutarate (2OG)-dependent oxygenase that catalyzes (3S)-lysyl hydroxylation. Crystallographic analyses reveal JMJD7 to be more closely related to the JmjC hydroxylases than to 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 that 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.