The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases
Biochemical, structural, and cellular studies reveal Jumonji-C (JmjC) domain-containing 7 (JMJD7) as a 2-oxoglutarate (2OG)-dependent oxygenase catalyzing a previously unreported type of post translational modification, (3S)-lysyl hydroxylation. Crystallographic analyses reveal JMJD7 as more close...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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| 格式: | Journal article |
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Springer Nature
2018
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| _version_ | 1826275699320684544 |
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| author | Markolovic, S Zhuang, Q Wilkins, SE Eaton, CD Abboud, MI Katz, MJ McNeil, HE Leśniak, R 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 |
| author_facet | Markolovic, S Zhuang, Q Wilkins, SE Eaton, CD Abboud, MI Katz, MJ McNeil, HE Leśniak, R 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 |
| author_sort | Markolovic, S |
| collection | OXFORD |
| description | Biochemical, structural, and cellular studies reveal Jumonji-C (JmjC) domain-containing 7 (JMJD7) as a 2-oxoglutarate (2OG)-dependent oxygenase catalyzing a previously unreported type of post translational modification, (3S)-lysyl hydroxylation. Crystallographic analyses reveal JMJD7 as more closely related to the JmjC hydroxylases rather than 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 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. |
| first_indexed | 2024-03-06T23:02:45Z |
| format | Journal article |
| id | oxford-uuid:62b9cef7-9260-4913-8914-346bd0d166bf |
| institution | University of Oxford |
| last_indexed | 2024-03-06T23:02:45Z |
| publishDate | 2018 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:62b9cef7-9260-4913-8914-346bd0d166bf2022-03-26T18:08:08ZThe Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPasesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:62b9cef7-9260-4913-8914-346bd0d166bfSymplectic Elements at OxfordSpringer Nature2018Markolovic, SZhuang, QWilkins, SEEaton, CDAbboud, MIKatz, MJMcNeil, HELeśniak, RHall, CStruwe, WBKonietzny, RDavis, SYang, MGe, WBenesch, JLPKessler, BMRatcliffe, PJCockman, MEFischer, RWappner, PChowdhury, RColeman, MSchofield, CJBiochemical, structural, and cellular studies reveal Jumonji-C (JmjC) domain-containing 7 (JMJD7) as a 2-oxoglutarate (2OG)-dependent oxygenase catalyzing a previously unreported type of post translational modification, (3S)-lysyl hydroxylation. Crystallographic analyses reveal JMJD7 as more closely related to the JmjC hydroxylases rather than 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 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. |
| spellingShingle | Markolovic, S Zhuang, Q Wilkins, SE Eaton, CD Abboud, MI Katz, MJ McNeil, HE Leśniak, R 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 The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases |
| title | The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases |
| title_full | The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases |
| title_fullStr | The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases |
| title_full_unstemmed | The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases |
| title_short | The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC GTPases |
| title_sort | jumonji c oxygenase jmjd7 catalyzes 3s lysyl hydroxylation of trafac gtpases |
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