(3S)-Lysyl hydroxylation of TRAFAC GTPases is catalyzed by the 1 Jumonji-C oxygenase JMJD7

ZHUANG Q; ABBOUD M I; LEśNIAK R K; COCKMAN M E; CHOWDHURY R; WILKINS SE; KATZ M J; HALL C; FISCHER R,; COLEMAN M L; MARKOLOVIC S; EATON C D; MCNEIL H E; RATCLIFFE PJ,; WAPPNER P; SCHOFIELD C J.

NATURE CHEMICAL BIOLOGY

NATURE PUBLISHING GROUP

Año: 2018 vol. 14 p. 688 - 695

1552-4450

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.