Interaction of JMJD6 with single-stranded RNA.
JMJD6 is a Jumonji C domain-containing hydroxylase. JMJD6 binds alpha-ketoglutarate and iron and has been characterized as either a histone arginine demethylase or U2AF65 lysyl hydroxylase. Here, we describe the structures of JMJD6 with and without alpha-ketoglutarate, which revealed a novel substrate binding groove and two positively charged surfaces. The structures also contain a stack of aromatic residues located near the active center. The side chain of one residue within this stack assumed different conformations in the two structures. Interestingly, JMJD6 bound efficiently to single-stranded RNA, but not to single-stranded DNA, double-stranded RNA, or double-stranded DNA. These structural features and truncation analysis of JMJD6 suggest that JMJD6 may bind and modify single-stand RNA rather than the previously reported peptide substrates.
Hong
Xia
X
Integrated Department of Immunology, National Jewish Health, Denver, CO 80206.
Zang
Jianye
J
White
Janice
J
Wang
Chao
C
Pan
Cheol-Ho
CH
Zhao
Rui
R
Murphy
Robert C
RC
Dai
Shaodong
S
Henson
Peter
P
Kappler
John W
JW
Hagman
James
J
Zhang
Gongyi
G
D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
D004277:DNA, Single-Stranded; D012330:RNA, Double-Stranded; D012313:RNA; D004247:DNA; D056484:Jumonji Domain-Containing Histone Demethylases; C524220:KDM6B protein, human