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Structural basis for MTA1c-mediated DNA N6-adenine methylation

Author

Listed:
  • Jiyun Chen

    (Xiamen University)

  • Rong Hu

    (Xiamen University)

  • Ying Chen

    (Xiamen University)

  • Xiaofeng Lin

    (Xiamen University)

  • Wenwen Xiang

    (Xiamen University)

  • Hong Chen

    (Xiamen University)

  • Canglin Yao

    (University of California, San Diego)

  • Liang Liu

    (Xiamen University)

Abstract

DNA N6-adenine methylation (6 mA) has recently been found to play a crucial role in epigenetic regulation in eukaryotes. MTA1c, a newly discovered 6 mA methyltransferase complex in ciliates, is composed of MTA1, MTA9, p1 and p2 subunits and specifically methylates ApT dinucleotides, yet its mechanism of action remains unknown. Here, we report the structures of Tetrahymena thermophila MTA1 (TthMTA1), Paramecium tetraurelia MTA9 (PteMTA9)-TthMTA1 binary complex, as well as the structures of TthMTA1-p1-p2 and TthMTA1-p2 complexes in apo, S-adenosyl methionine-bound and S-adenosyl homocysteine-bound states. We show that MTA1 is the catalytically active subunit, p1 and p2 are involved in the formation of substrate DNA-binding channel, and MTA9 plays a structural role in the stabilization of substrate binding. We identify that MTA1 is a cofactor-dependent catalytically active subunit, which exhibits stable SAM-binding activity only after assembly with p2. Our structures and corresponding functional studies provide a more detailed mechanistic understanding of 6 mA methylation.

Suggested Citation

  • Jiyun Chen & Rong Hu & Ying Chen & Xiaofeng Lin & Wenwen Xiang & Hong Chen & Canglin Yao & Liang Liu, 2022. "Structural basis for MTA1c-mediated DNA N6-adenine methylation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31060-6
    DOI: 10.1038/s41467-022-31060-6
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    References listed on IDEAS

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    1. John R. Horton & Clayton B. Woodcock & Sifa B. Opot & Norbert O. Reich & Xing Zhang & Xiaodong Cheng, 2019. "The cell cycle-regulated DNA adenine methyltransferase CcrM opens a bubble at its DNA recognition site," Nature Communications, Nature, vol. 10(1), pages 1-9, December.
    2. Tao P. Wu & Tao Wang & Matthew G. Seetin & Yongquan Lai & Shijia Zhu & Kaixuan Lin & Yifei Liu & Stephanie D. Byrum & Samuel G. Mackintosh & Mei Zhong & Alan Tackett & Guilin Wang & Lawrence S. Hon & , 2016. "DNA methylation on N6-adenine in mammalian embryonic stem cells," Nature, Nature, vol. 532(7599), pages 329-333, April.
    3. Da Jia & Renata Z. Jurkowska & Xing Zhang & Albert Jeltsch & Xiaodong Cheng, 2007. "Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation," Nature, Nature, vol. 449(7159), pages 248-251, September.
    4. Yogesh K. Gupta & Siu-Hong Chan & Shuang-yong Xu & Aneel K. Aggarwal, 2015. "Structural basis of asymmetric DNA methylation and ATP-triggered long-range diffusion by EcoP15I," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    5. Xiang Wang & Jing Feng & Yuan Xue & Zeyuan Guan & Delin Zhang & Zhu Liu & Zhou Gong & Qiang Wang & Jinbo Huang & Chun Tang & Tingting Zou & Ping Yin, 2016. "Structural basis of N6-adenosine methylation by the METTL3–METTL14 complex," Nature, Nature, vol. 534(7608), pages 575-578, June.
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    1. Carlos Lax & Stephen J. Mondo & Macario Osorio-Concepción & Anna Muszewska & María Corrochano-Luque & Gabriel Gutiérrez & Robert Riley & Anna Lipzen & Jie Guo & Hope Hundley & Mojgan Amirebrahimi & Vi, 2024. "Symmetric and asymmetric DNA N6-adenine methylation regulates different biological responses in Mucorales," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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