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

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Authors

  • Suzana Markolovic
  • Sarah E. Wilkins
  • Charlotte Eaton
  • Martine I. Abboud
  • Maximiliano J. Katz
  • Robert K. Leśniak
  • 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 Wappner
  • Rasheduzzaman Chowdhury
  • Christopher J. Schofield

Abstract

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.

Details

Original languageEnglish
Pages (from-to)688-695
Number of pages8
JournalNature Chemical Biology
Volume14
Issue number7
Early online date18 Jun 2018
Publication statusPublished - Jul 2018