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TitleStructural and functional insights into the T-even type bacteriophage topoisomerase II.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 8719, Year 2024
Publish dateOct 8, 2024
AuthorsYuhui Xin / Runqi Xian / Yunge Yang / Jingyuan Cong / Zihe Rao / Xuemei Li / Yutao Chen /
PubMed AbstractT-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 ...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.
External linksNat Commun / PubMed:39379365 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.8 - 6.8 Å
Structure data

EMDB-39391, PDB-8ylu:
structure of phage T6 topoisomerase II central domain bound with DNA
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-39433, PDB-8yo1:
structure of phage T6 topoisomerase II ATPase domain bound with AMPPNP
Method: EM (single particle) / Resolution: 3.55 Å

EMDB-39434, PDB-8yo3:
structure of phage T4 topoisomerase II central domain
Method: EM (single particle) / Resolution: 3.62 Å

EMDB-39435, PDB-8yo4:
structure of phage T4 topoisomerase II central domain bound with DNA
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-39436, PDB-8yo5:
structure of phage T6 topoisomerase II central domain
Method: EM (single particle) / Resolution: 3.93 Å

EMDB-39437, PDB-8yo7:
structure of phage T6 topoisomerase II central domain bound with DNA and m-AMSA
Method: EM (single particle) / Resolution: 3.16 Å

EMDB-39438, PDB-8yo9:
structure of phage T4 topoisomerase II gp52 subunit WHD-open state
Method: EM (single particle) / Resolution: 6.12 Å

EMDB-39444, PDB-8yod:
structure of phage T6 apo full-length topoisomerase II
Method: EM (single particle) / Resolution: 6.8 Å

EMDB-39454, PDB-8yon:
structure of phage T6 full-length topoisomerase II bound with DNA
Method: EM (single particle) / Resolution: 6.73 Å

PDB-9imj:
Bacteriophage T6 topoisomerase II ATPase domain crystal strcuture
Method: X-RAY DIFFRACTION / Resolution: 2.8 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

ChemComp-ASW:
N-[4-(acridin-9-ylamino)-3-methoxyphenyl]methanesulfonamide

ChemComp-HOH:
WATER

Source
  • enterobacteria phage t6 (virus)
  • escherichia phage t4 (virus)
  • salmonella phage chi (virus)
  • dna molecule (others)
  • Enterobacteria phage T4 (virus)
KeywordsISOMERASE / topoisomerase II / topoisomerase II ATPase domain

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