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  Wappner; Rasheduzzaman  Chowdhury; Mathew Coleman; Christopher J.  Schofield

doi:10.1038/s41589-018-0071-y

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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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.

Original language	English
Pages (from-to)	688-695
Number of pages	8
Journal	Nature Chemical Biology
Volume	14
Issue number	7
Early online date	18 Jun 2018
DOIs	https://doi.org/10.1038/s41589-018-0071-y
Publication status	Published - Jul 2018

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Markolovic, S., Zhuang, Q., Wilkins, S. E., Eaton, C., Abboud, M. I., Katz, M. J., McNeil, H., Leśniak, R. K., Hall, C., Struwe, W. B., Konietzny, R., Davis, S., Yang, M., Ge, W., Benesch, J. L. P., Kessler, B. M., Ratcliffe, P. J., Cockman, M. E., Fischer, R., ... Schofield, C. J. (2018). The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases. Nature Chemical Biology, 14(7), 688-695. Advance online publication. https://doi.org/10.1038/s41589-018-0071-y

@article{3a1e769c15d6473286b3ffa2a421f784,

title = "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) 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.",

author = "Suzana Markolovic and Qinqin Zhuang and Wilkins, {Sarah E.} and Charlotte Eaton and Abboud, {Martine I.} and Katz, {Maximiliano J.} and Helen McNeil and Le{\'s}niak, {Robert K.} and Charlotte Hall and Struwe, {Weston B.} and Rebecca Konietzny and Simon Davis and Ming Yang and Wei Ge and Benesch, {Justin L P} and Kessler, {Benedikt M.} and Ratcliffe, {Peter J.} and Cockman, {Matthew E.} and Roman Fischer and Pablo Wappner and Rasheduzzaman Chowdhury and Mathew Coleman and Schofield, {Christopher J.}",

year = "2018",

month = jul,

doi = "10.1038/s41589-018-0071-y",

language = "English",

volume = "14",

pages = "688--695",

journal = "Nature Chemical Biology",

issn = "1552-4450",

publisher = "Nature Publishing Group",

number = "7",

}

Markolovic, S, Zhuang, Q, Wilkins, SE, Eaton, C, Abboud, MI, Katz, MJ, McNeil, H, Leśniak, RK, 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 2018, 'The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases', Nature Chemical Biology, vol. 14, no. 7, pp. 688-695. https://doi.org/10.1038/s41589-018-0071-y

TY - JOUR

T1 - The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases

AU - Markolovic, Suzana

AU - Zhuang, Qinqin

AU - Wilkins, Sarah E.

AU - Eaton, Charlotte

AU - Abboud, Martine I.

AU - Katz, Maximiliano J.

AU - McNeil, Helen

AU - Leśniak, Robert K.

AU - Hall, Charlotte

AU - Struwe, Weston B.

AU - Konietzny, Rebecca

AU - Davis, Simon

AU - Yang, Ming

AU - Ge, Wei

AU - Benesch, Justin L P

AU - Kessler, Benedikt M.

AU - Ratcliffe, Peter J.

AU - Cockman, Matthew E.

AU - Fischer, Roman

AU - Wappner, Pablo

AU - Chowdhury, Rasheduzzaman

AU - Coleman, Mathew

AU - Schofield, Christopher J.

PY - 2018/7

Y1 - 2018/7

N2 - 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.

AB - 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.

U2 - 10.1038/s41589-018-0071-y

DO - 10.1038/s41589-018-0071-y

M3 - Article

SN - 1552-4450

VL - 14

SP - 688

EP - 695

JO - Nature Chemical Biology

JF - Nature Chemical Biology

IS - 7

ER -

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

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