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

Autor: Pablo Wappner, Helen E McNeil, Robert K. Leśniak, Martine I. Abboud, Wei Ge, Rasheduzzaman Chowdhury, Simon J. Davis, Charlotte A. Hall, Weston B. Struwe, Ming Yang, Rebecca Konietzny, Peter J. Ratcliffe, Christopher J. Schofield, Sarah E. Wilkins, Charlotte D. Eaton, Roman Fischer, Suzana Markolovic, Maximiliano Javier Katz, Qinqin Zhuang, Justin L. P. Benesch, Benedikt M. Kessler, Mathew L. Coleman, Matthew E. Cockman
Rok vydání: 2018
Předmět:
Zdroj: CONICET Digital (CONICET)
Consejo Nacional de Investigaciones Científicas y Técnicas
instacron:CONICET
Nature chemical biology
ISSN: 1552-4469
1552-4450
Popis: 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. Fil: Markolovic, Suzana. University of Oxford; Reino Unido Fil: Zhuang, Qinqin. University Of Birmingham; Reino Unido Fil: Wilkins, Sarah E.. University of Oxford; Reino Unido Fil: Eaton, Charlotte D.. University Of Birmingham; Reino Unido Fil: Abboud, Martine I.. University of Oxford; Reino Unido Fil: Katz, Maximiliano Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: McNeil, Helen E.. University Of Birmingham; Reino Unido Fil: Leśniak, Robert K.. University of Oxford; Reino Unido Fil: Hall, Charlotte. University Of Birmingham; Reino Unido Fil: Struwe, Weston B.. University of Oxford; Reino Unido Fil: Konietzny, Rebecca. University of Oxford; Reino Unido Fil: Davis, Simon. University of Oxford; Reino Unido Fil: Yang, Ming. The Francis Crick Institute; Reino Unido. University of Oxford; Reino Unido Fil: Ge, Wei. University of Oxford; Reino Unido Fil: Benesch, Justin L. P.. University of Oxford; Reino Unido Fil: Kessler, Benedikt M.. University of Oxford; Reino Unido Fil: Ratcliffe, Peter J.. University of Oxford; Reino Unido. The Francis Crick Institute; Reino Unido Fil: Cockman, Matthew E.. The Francis Crick Institute; Reino Unido. University of Oxford; Reino Unido Fil: Fischer, Roman. University of Oxford; Reino Unido Fil: Wappner, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Chowdhury, Rasheduzzaman. University of Stanford; Estados Unidos. University of Oxford; Reino Unido Fil: Coleman, Mathew L.. University Of Birmingham; Reino Unido Fil: Schofield, Christopher J.. University of Oxford; Reino Unido
Databáze: OpenAIRE
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