Molecular insights into DNA recognition and methylation by non-canonical type I restriction-modification systems

Jingpeng Zhu, Yina Gao, Yong Wang, Qi Zhan, Han Feng, Xiu Luo, Peipei Li, Songqing Liu, Hai Hou () and Pu Gao ()
Additional contact information
Jingpeng Zhu: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Yina Gao: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Yong Wang: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Qi Zhan: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Han Feng: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Xiu Luo: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Peipei Li: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Songqing Liu: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Hai Hou: Northwestern Polytechnical University
Pu Gao: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract Type I restriction-modification systems help establish the prokaryotic DNA methylation landscape and provide protection against invasive DNA. In addition to classical m6A modifications, non-canonical type I enzymes catalyze both m6A and m4C using alternative DNA-modification subunits M1 and M2. Here, we report the crystal structures of the non-canonical PacII_M1M2S methyltransferase bound to target DNA and reaction product S-adenosylhomocysteine in a closed clamp-like conformation. Target DNA binds tightly within the central tunnel of the M1M2S complex and forms extensive contacts with all three protein subunits. Unexpectedly, while the target cytosine properly inserts into M2’s pocket, the target adenine (either unmethylated or methylated) is anchored outside M1’s pocket. A unique asymmetric catalysis is established where PacII_M1M2S has precisely coordinated the relative conformations of different subunits and evolved specific amino acids within M2/M1. This work provides insights into mechanisms of m6A/m4C catalysis and guidance for designing tools based on type I restriction-modification enzymes.

Date: 2022
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-022-34085-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34085-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-34085-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().