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TitleDirect trapping of the transport-segment DNA by the central domain of type IIA topoisomerases.
Journal, issue, pagesSci Adv, Vol. 11, Issue 51, Page eadw2839, Year 2025
Publish dateDec 19, 2025
AuthorsYuhui Xin / Runqi Xian / Congrong Liu / Oujia Zhang / Zihe Rao / Xuemei Li / Yutao Chen /
PubMed AbstractType IIA topoisomerases modulate DNA topology by coordinating the cleavage of gate-segment DNA and the passage of transport-segment DNA-a mechanism conserved across species and essential for diverse ...Type IIA topoisomerases modulate DNA topology by coordinating the cleavage of gate-segment DNA and the passage of transport-segment DNA-a mechanism conserved across species and essential for diverse cellular processes. While gate-segment interactions have been extensively studied, direct structural evidence of transport-segment capture has remained elusive, limiting our understanding of the full catalytic cycle. Here, we present a cryo-electron microscopy structure of the T4 bacteriophage topoisomerase II with a transport-segment DNA bound directly to its central domain. The structure reveals conformational rearrangements in the central domain that accommodate the transport-segment DNA, suggesting an alternative sequence of events in which the enzyme sliding along the loosely bound religated gate segment may precede transport-segment passage through the coiled-coil gate. Supported by mutational and biochemical assays, our findings provide previously unidentified mechanistic insights and open potential avenues for the development of next-generation type IIA topoisomerase inhibitors.
External linksSci Adv / PubMed:41406217 / PubMed Central
MethodsEM (single particle)
Resolution3.03 - 3.09 Å
Structure data

61621

9jnk

EMDB-61621, PDB-9jnk:
Bacteriophage T4 topoisomerse II bound with a T-segment DNA
Method: EM (single particle) / Resolution: 3.03 Å

61683

9jor

EMDB-61683, PDB-9jor:
structure of phage T4 topoisomerase II central domain bound with DNA
Method: EM (single particle) / Resolution: 3.09 Å

63118

9lii

EMDB-63118, PDB-9lii:
structure of phage T4 topoisomerase II central domain
Method: EM (single particle) / Resolution: 3.06 Å

Chemicals

ChemComp-MG:
Unknown entry

Source
  • enterobacteria phage t4 (virus)
  • escherichia phage t4 (virus)
  • dna molecule (others)
  • homo sapiens (human)
KeywordsISOMERASE/DNA / Type IIA topoisomerase / T-segment DNA / ISOMERASE-DNA complex / ISOMERASE / topoisomerase II

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