Structural and functional insights into the T-even type bacteriophage topoisomerase II.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
08 Oct 2024
Historique:
received: 23 04 2024
accepted: 26 09 2024
medline: 9 10 2024
pubmed: 9 10 2024
entrez: 8 10 2024
Statut: epublish

Résumé

T-even type bacteriophages are virulent phages commonly used as model organisms, playing a crucial role in understanding various biological processes. One such process involves the regulation of DNA topology during phage replication upon host infection, governed by type IIA DNA topoisomerases. In spite of various studies on prokaryotic and eukaryotic counterparts, viral topoisomerase II remains insufficiently understood, especially the unique domain composition of T4 phage. In this study, we determine the cryo-EM structures of topoisomerase II from T4 and T6 phages, including full-length structures of both apo and DNA-binding states which have never been determined before. Together with other conformational states, these structures provide an explicit blueprint of mechanisms of phage topoisomerase II. Particularly, the asymmetric dimeric interactions observed in cryo-EM structures of T6 phage topoisomerase II ATPase domain and central domain bound with DNA shed light on the asynchronous ATP usage and asynchronous cleavage of the G-segment DNA, respectively. The elucidation of phage topoisomerase II's structures and functions not only enhances our understanding of mechanisms and evolutionary parallels with prokaryotic and eukaryotic homologs but also highlights its potential as a model for developing type IIA topoisomerase inhibitors.

Identifiants

pubmed: 39379365
doi: 10.1038/s41467-024-53037-3
pii: 10.1038/s41467-024-53037-3
doi:

Substances chimiques

DNA Topoisomerases, Type II EC 5.99.1.3
DNA, Viral 0
Viral Proteins 0
Adenosine Triphosphate 8L70Q75FXE

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

8719

Informations de copyright

© 2024. The Author(s).

Références

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Auteurs

Yuhui Xin (Y)

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.

Runqi Xian (R)

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.

Yunge Yang (Y)

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.

Jingyuan Cong (J)

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.

Zihe Rao (Z)

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. Raozh@ibp.ac.cn.
Laboratory of Structural Biology, School of Medicine, Tsinghua University, Beijing, China. Raozh@ibp.ac.cn.

Xuemei Li (X)

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. lixm@ibp.ac.cn.

Yutao Chen (Y)

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. chenyutao@ibp.ac.cn.

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