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Structure paper

TitleCryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 4620, Year 2024
Publish dateMay 30, 2024
AuthorsLu Xue / Tiancai Chang / Zimu Li / Chenchen Wang / Heyu Zhao / Mei Li / Peng Tang / Xin Wen / Mengmeng Yu / Jiqin Wu / Xichen Bao / Xiaojun Wang / Peng Gong / Jun He / Xinwen Chen / Xiaoli Xiong /
PubMed AbstractInfluenza viruses and thogotoviruses account for most recognized orthomyxoviruses. Thogotoviruses, exemplified by Thogoto virus (THOV), are capable of infecting humans using ticks as vectors. THOV ...Influenza viruses and thogotoviruses account for most recognized orthomyxoviruses. Thogotoviruses, exemplified by Thogoto virus (THOV), are capable of infecting humans using ticks as vectors. THOV transcribes mRNA without the extraneous 5' end sequences derived from cap-snatching in influenza virus mRNA. Here, we report cryo-EM structures to characterize THOV polymerase RNA synthesis initiation and elongation. The structures demonstrate that THOV RNA transcription and replication are able to start with short dinucleotide primers and that the polymerase cap-snatching machinery is likely non-functional. Triggered by RNA synthesis, asymmetric THOV polymerase dimers can form without the involvement of host factors. We confirm that, distinctive from influenza viruses, THOV-polymerase RNA synthesis is weakly dependent of the host factors ANP32A/B/E in human cells. This study demonstrates varied mechanisms in RNA synthesis and host factor utilization among orthomyxoviruses, providing insights into the mechanisms behind thogotoviruses' broad-infectivity range.
External linksNat Commun / PubMed:38816392 / PubMed Central
MethodsEM (single particle)
Resolution2.3 - 3.16 Å
Structure data

EMDB-39838, PDB-8z85:
Cryo-EM structure of Thogoto virus polymerase in transcription pre-initiation conformation 1
Method: EM (single particle) / Resolution: 2.3 Å

EMDB-39848, PDB-8z8j:
Cryo-EM structure of Thogoto virus polymerase in transcription pre-initiation conformation 2
Method: EM (single particle) / Resolution: 3.16 Å

EMDB-39849, PDB-8z8n:
Cryo-EM structure of Thogoto virus polymerase in transcription pre-initiation conformation 3
Method: EM (single particle) / Resolution: 2.79 Å

EMDB-39850, PDB-8z8x:
Cryo-EM structure of Thogoto virus polymerase in a transcription initiation conformation
Method: EM (single particle) / Resolution: 3.06 Å

EMDB-39852, PDB-8z90:
Cryo-EM structure of Thogoto virus polymerase in transcription initiation conformation 2
Method: EM (single particle) / Resolution: 2.87 Å

EMDB-39855, PDB-8z97:
Cryo-EM structure of Thogoto virus polymerase in a transcription elongation conformation
Method: EM (single particle) / Resolution: 2.65 Å

EMDB-39856, PDB-8z98:
Cryo-EM structure of Thogoto virus polymerase in a transcription reception conformation
Method: EM (single particle) / Resolution: 2.52 Å

EMDB-39862, PDB-8z9h:
Cryo-EM structure of Thogoto virus polymerase in a transcription elongation-reception conformation
Method: EM (single particle) / Resolution: 2.7 Å

EMDB-39867, PDB-8z9q:
Cryo-EM structure of Thogoto virus polymerase in a replication reception conformation
Method: EM (single particle) / Resolution: 2.33 Å

EMDB-39868, PDB-8z9r:
Cryo-EM structure of Thogoto virus polymerase in a replication elongation-reception conformation
Method: EM (single particle) / Resolution: 2.58 Å

Chemicals

ChemComp-G2P:
PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER / GMP-CPP, energy-carrying molecule analogue*YM

ChemComp-V9G:
7-METHYL-GUANOSINE-5'-TRIPHOSPHATE-5'-(2'-O-METHYL)-ADENOSINE

Source
  • thogoto virus (isolate siar 126)
KeywordsTRANSCRIPTION / RNA virus Polymerase / RNA polymerase

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