The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases

Suzana Markolovic, Qinqin Zhuang, Sarah E. Wilkins, Charlotte Eaton, Martine I. Abboud, Maximiliano J. Katz, Helen McNeil, Robert K. Leśniak, Charlotte Hall, Weston B. Struwe, Rebecca Konietzny, Simon Davis, Ming Yang, Wei Ge, Justin L P Benesch, Benedikt M. Kessler, Peter J. Ratcliffe, Matthew E. Cockman, Roman Fischer, Pablo WappnerRasheduzzaman Chowdhury, Mathew Coleman, Christopher J. Schofield

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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.
Original languageEnglish
Pages (from-to)688-695
Number of pages8
JournalNature Chemical Biology
Issue number7
Early online date18 Jun 2018
Publication statusPublished - Jul 2018


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