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Structure paper

TitleStructural insights into human topoisomerase 3β DNA and RNA catalysis and nucleic acid gate dynamics.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 834, Year 2025
Publish dateJan 19, 2025
AuthorsXi Yang / Xuemin Chen / Wei Yang / Yves Pommier /
PubMed AbstractType IA topoisomerases (TopoIAs) are present in all living organisms. They resolve DNA/RNA catenanes, knots and supercoils by breaking and rejoining single-stranded DNA/RNA segments and allowing the ...Type IA topoisomerases (TopoIAs) are present in all living organisms. They resolve DNA/RNA catenanes, knots and supercoils by breaking and rejoining single-stranded DNA/RNA segments and allowing the passage of another nucleic acid segment through the break. Topoisomerase III-β (TOP3B), the only RNA topoisomerase in metazoans, promotes R-loop disassembly and translation of mRNAs. Defects in TOP3B lead to severe neurological diseases. We present a series of cryo-EM structures of human TOP3B with its cofactor TDRD3 during cleavage and rejoining of DNA or RNA, thus elucidating the roles of divalent metal ions and key enzyme residues in each step of the catalytic cycle. We also obtained the structure of an open-gate configuration that addresses the long-standing question of the strand-passage mechanism. Our studies reveal how TOP3B catalyzes both DNA and RNA relaxation, while TOP3A acts only on DNA.
External linksNat Commun / PubMed:39828754 / PubMed Central
MethodsEM (single particle)
Resolution3.01 - 4.25 Å
Structure data

45374

9c9w

EMDB-45374, PDB-9c9w:
Dimerized human TOP3B-TDRD3 core complex with a DNA mismatch bubble
Method: EM (single particle) / Resolution: 4.25 Å

45376

9c9y

EMDB-45376, PDB-9c9y:
Human TOP3B-TDRD3 core complex in DNA pre-cleavage state
Method: EM (single particle) / Resolution: 3.35 Å

45378

9ca0

EMDB-45378, PDB-9ca0:
Human TOP3B-TDRD3 core complex in DNA post-cleavage state
Method: EM (single particle) / Resolution: 3.48 Å

45379

9ca1

EMDB-45379, PDB-9ca1:
Human TOP3B-TDRD3 core complex in DNA religation state
Method: EM (single particle) / Resolution: 3.26 Å

45380

9ca4

EMDB-45380, PDB-9ca4:
Human TOP3B-TDRD3 core complex in RNA rejoining state
Method: EM (single particle) / Resolution: 3.01 Å

45390

9cag

EMDB-45390, PDB-9cag:
Human TOP3B-TDRD3 core complex in RNA pre-cleavage state
Method: EM (single particle) / Resolution: 3.33 Å

45391

9cah

EMDB-45391, PDB-9cah:
Human TOP3B-TDRD3 complex
Method: EM (single particle) / Resolution: 3.16 Å

45393

9caj

EMDB-45393, PDB-9caj:
Human TOP3B-TDRD3 core complex in pre-cleavage state with ssDNA 5'-ACAGATATT-3
Method: EM (single particle) / Resolution: 3.51 Å

45394

9cak

EMDB-45394, PDB-9cak:
Human TOP3B-TDRD3 core complex in DNA rejoining state with ssDNA 5'-GACAGATATT-3
Method: EM (single particle) / Resolution: 3.01 Å

45395

9cal

EMDB-45395, PDB-9cal:
Human TOP3B-TDRD3 core complex in post-cleavage state with ssDNA 5'-ACAGATATT-3
Method: EM (single particle) / Resolution: 3.15 Å

Chemicals

ChemComp-MN:
Unknown entry

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
KeywordsISOMERASE/DNA / Topoisomerase / DNA / Supercoiling / ISOMERASE-DNA complex / ISOMERASE/RNA / ISOMERASE-RNA complex / ISOMERASE

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