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-Structure paper
| タイトル | Mechanism for the substrate recognition by a eukaryotic DNA N-adenine methyltransferase complex. |
|---|---|
| ジャーナル・号・ページ | Nat Commun, Vol. 16, Issue 1, Page 8690, Year 2025 |
| 掲載日 | 2025年9月30日 |
著者 | Qi Xu / Ying Xie / Zhubing Shi / ![]() |
| PubMed 要旨 | In eukaryotes, DNA N-methyladenine (6mA) modification plays important roles in various cellular functions, such as chromatin dynamics, gene expression regulation, and DNA damage response. It remains ...In eukaryotes, DNA N-methyladenine (6mA) modification plays important roles in various cellular functions, such as chromatin dynamics, gene expression regulation, and DNA damage response. It remains largely unknown how eukaryotic DNA 6mA methyltransferases (MTases) recognize their substrates. Here, we reported the structures of DNA-bound eukaryotic 6mA MTase complexes. The MTA1 complex (MTA1c) in ciliates is composed of MTA1, MTA9 (or MTA9-B), p1 and p2 subunits. Cryo-electron microscopy structures of MTA1c-DNA complexes reveal that DNA lies on the surface of the MTA1-MTA9/9-B dimer and is clamped by the p1 N-terminal region. The target deoxyadenosine is flipped out of the DNA duplex and approaches the catalytic center. Unmethylated and hemi-methylated DNA substrates bind MTA1c with differential conformational dynamics. Our structural and biochemical studies shed light on the activation and substrate recognition of MTA1c and provide a framework for understanding the molecular mechanism of DNA 6mA modification in eukaryotes. |
リンク | Nat Commun / PubMed:41027852 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.54 - 3.29 Å |
| 構造データ | EMDB-38777, PDB-8xyl: EMDB-38780, PDB-8xyp: EMDB-38781, PDB-8xyq: EMDB-38782, PDB-8xyx: ![]() EMDB-38786: Cryo-EM structure of DNA-bound Tetrahymena DNA methyltransferase complex MTA1c ![]() EMDB-38787: Cryo-EM structure of DNA-bound Tetrahymena DNA methyltransferase complex MTA1c EMDB-63956, PDB-9u92: EMDB-63961, PDB-9u9e: EMDB-63963: Cryo-EM structure of DNA-bound Tetrahymena DNA methyltransferase complex MTA1c (MTA9-B) EMDB-63967, PDB-9u9k: ![]() EMDB-63970: Cryo-EM structure of DNA-bound Tetrahymena DNA methyltransferase complex MTA1c |
| 化合物 | ![]() ChemComp-SAH: ![]() ChemComp-SAM: |
| 由来 |
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キーワード | DNA BINDING PROTEIN / DNA methyltransferase / DNA N6-methyladenine modification / chromatin regulation / gene regulation / protein-DNA complex / DNA BINDING PROTEIN/DNA / DNA BINDING PROTEIN-DNA complex |
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tetrahymena thermophila sb210 (真核生物)
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