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The cell cycle-regulated DNA adenine methyltransferase CcrM opens a bubble at its DNA recognition site

Author

Listed:
  • John R. Horton

    (University of Texas MD Anderson Cancer Center)

  • Clayton B. Woodcock

    (University of Texas MD Anderson Cancer Center)

  • Sifa B. Opot

    (University of Texas MD Anderson Cancer Center)

  • Norbert O. Reich

    (University of California)

  • Xing Zhang

    (University of Texas MD Anderson Cancer Center)

  • Xiaodong Cheng

    (University of Texas MD Anderson Cancer Center)

Abstract

The Caulobacter crescentus cell cycle-regulated DNA methyltransferase (CcrM) methylates the adenine of hemimethylated GANTC after replication. Here we present the structure of CcrM in complex with double-stranded DNA containing the recognition sequence. CcrM contains an N-terminal methyltransferase domain and a C-terminal nonspecific DNA-binding domain. CcrM is a dimer, with each monomer contacting primarily one DNA strand: the methyltransferase domain of one molecule binds the target strand, recognizes the target sequence, and catalyzes methyl transfer, while the C-terminal domain of the second molecule binds the non-target strand. The DNA contacts at the 5-base pair recognition site results in dramatic DNA distortions including bending, unwinding and base flipping. The two DNA strands are pulled apart, creating a bubble comprising four recognized base pairs. The five bases of the target strand are recognized meticulously by stacking contacts, van der Waals interactions and specific Watson–Crick polar hydrogen bonds to ensure high enzymatic specificity.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12498-7
    DOI: 10.1038/s41467-019-12498-7
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    Cited by:

    1. 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.
    2. Richard Quintana-Feliciano & Jithesh Kottur & Mi Ni & Rikhia Ghosh & Leslie Salas-Estrada & Goran Ahlsen & Olga Rechkoblit & Lawrence Shapiro & Marta Filizola & Gang Fang & Aneel K. Aggarwal, 2024. "Burkholderia cenocepacia epigenetic regulator M.BceJIV simultaneously engages two DNA recognition sequences for methylation," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

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