4NM6

Crystal structure of TET2-DNA complex

Summary for 4NM6

• Entry DOI: 10.2210/pdb4nm6/pdb
• Descriptor: Methylcytosine dioxygenase TET2, 5'-D(*AP*CP*CP*AP*CP*(5CM)P*GP*GP*TP*GP*GP*T)-3', ZINC ION, ... (6 entities in total)
• Functional Keywords: dna hydroxylation, oxidoreductase-dna complex, oxidoreductase/dna
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 59208.39

Authors

Hu, L.,Li, Z.,Cheng, J.,Rao, Q.,Gong, W.,Liu, M.,Wang, P.,Xu, Y. (deposition date: 2013-11-14, release date: 2013-12-18, Last modification date: 2024-02-28)

Primary citation

Hu, L.,Li, Z.,Cheng, J.,Rao, Q.,Gong, W.,Liu, M.,Shi, Y.G.,Zhu, J.,Wang, P.,Xu, Y.
Crystal Structure of TET2-DNA Complex: Insight into TET-Mediated 5mC Oxidation.
Cell(Cambridge,Mass.), 155:1545-1555, 2013

PubMed Abstract: TET proteins oxidize 5-methylcytosine (5mC) on DNA and play important roles in various biological processes. Mutations of TET2 are frequently observed in myeloid malignance. Here, we present the crystal structure of human TET2 bound to methylated DNA at 2.02 Å resolution. The structure shows that two zinc fingers bring the Cys-rich and DSBH domains together to form a compact catalytic domain. The Cys-rich domain stabilizes the DNA above the DSBH core. TET2 specifically recognizes CpG dinucleotide and shows substrate preference for 5mC in a CpG context. 5mC is inserted into the catalytic cavity with the methyl group orientated to catalytic Fe(II) for reaction. The methyl group is not involved in TET2-DNA contacts so that the catalytic cavity allows TET2 to accommodate 5mC derivatives for further oxidation. Mutations of Fe(II)/NOG-chelating, DNA-interacting, and zinc-chelating residues are frequently observed in human cancers. Our studies provide a structural basis for understanding the mechanisms of TET-mediated 5mC oxidation.

PubMed: 24315485
DOI: 10.1016/j.cell.2013.11.020

Experimental method

X-RAY DIFFRACTION (2.026 Å)