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TitleTranscription regulation of African swine fever virus: dual role of M1249L.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 10058, Year 2024
Publish dateNov 20, 2024
AuthorsDongming Zhao / Nan Wang / Xiaoying Feng / Zhenjiang Zhang / Kongen Xu / Tao Zheng / Yunge Yang / Xuemei Li / Xianjin Ou / Rui Zhao / Zihe Rao / Zhigao Bu / Yutao Chen / Xiangxi Wang /
PubMed AbstractAfrican swine fever virus (ASFV), which poses significant risks to the global economy, encodes a unique host-independent transcription system. This system comprises an eight-subunit RNA polymerase ...African swine fever virus (ASFV), which poses significant risks to the global economy, encodes a unique host-independent transcription system. This system comprises an eight-subunit RNA polymerase (vRNAP), temporally expressed transcription factors and transcript associated proteins, facilitating cross-species transmission via intermediate host. The protein composition of the virion and the presence of transcription factors in virus genome suggest existence of distinct transcription systems during viral infection. However, the precise mechanisms of transcription regulation remain elusive. Through analyses of dynamic transcriptome, vRNAP-associated components and cell-based assay, the critical role of M1249L in viral transcription regulation has been highlighted. Atomic-resolution structures of vRNAP-M1249L supercomplex, exhibiting a variety of conformations, have uncovered the dual functions of M1249L. During early transcription, M1249L could serve as multiple temporary transcription factors with C-terminal domain acting as a switcher for activation/inactivation, while during late transcription it aids in the packaging of the transcription machinery. The structural and functional characteristics of M1249L underscore its vital roles in ASFV transcription, packaging, and capsid assembly, presenting novel opportunities for therapeutic intervention.
External linksNat Commun / PubMed:39567541 / PubMed Central
MethodsEM (single particle)
Resolution2.56 - 9.32 Å
Structure data

EMDB-39505, PDB-8yqt:
African swine fever virus RNA Polymerase-M1249L complex2
Method: EM (single particle) / Resolution: 2.56 Å

EMDB-39506, PDB-8yqu:
African swine fever virus RNA Polymerase-M1249L complex1
Method: EM (single particle) / Resolution: 2.85 Å

EMDB-39507, PDB-8yqv:
African swine fever virus RNA Polymerase core
Method: EM (single particle) / Resolution: 2.67 Å

EMDB-39508, PDB-8yqw:
ASFV RNA polymerase-M1249L complex3
Method: EM (single particle) / Resolution: 2.68 Å

EMDB-39509, PDB-8yqx:
ASFV RNA polymerase-M1249L complex4
Method: EM (single particle) / Resolution: 2.97 Å

EMDB-39510, PDB-8yqy:
ASFV RNA polymerase-M1249L complex complete
Method: EM (single particle) / Resolution: 3.68 Å

EMDB-39511, PDB-8yqz:
African swine fever virus RNA Polymerase--DNA complex
Method: EM (single particle) / Resolution: 2.78 Å

EMDB-39512: ASFV RNA polymerase-M1249L complex 6
Method: EM (single particle) / Resolution: 9.23 Å

EMDB-39513: ASFV RNA polymerase-M1249L complex 7
Method: EM (single particle) / Resolution: 5.17 Å

EMDB-39514: ASFV RNA polymerase-M1249L complex 5
Method: EM (single particle) / Resolution: 3.23 Å

EMDB-39515: ASFV RNA polymerase-M1249L complex 9
Method: EM (single particle) / Resolution: 4.04 Å

EMDB-39516: ASFV RNA polymerase-M1249L complex 8
Method: EM (single particle) / Resolution: 3.19 Å

EMDB-39517: ASFV RNA polymerase-M1249L complex10
Method: EM (single particle) / Resolution: 3.49 Å

EMDB-39518: ASFV RNA polymerase-M1249L complex11
Method: EM (single particle) / Resolution: 4.17 Å

EMDB-39519: ASFV RNA polymerase-M1249L complex 12
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-39520: ASFV RNA polymerase-M1249L complex14
Method: EM (single particle) / Resolution: 3.91 Å

EMDB-39521: ASFV RNA polymerase-M1249L complex 13
Method: EM (single particle) / Resolution: 9.32 Å

EMDB-39522: ASFV RNA polymerase-M1249L complex 15
Method: EM (single particle) / Resolution: 4.53 Å

EMDB-39523: ASFV RNA polymerase-M1249L complex 16
Method: EM (single particle) / Resolution: 3.59 Å

EMDB-39524: ASFV RNA polymerase-M1249L complex 17
Method: EM (single particle) / Resolution: 3.31 Å

EMDB-39525: ASFV RNA polymerase-M1249L complex 18
Method: EM (single particle) / Resolution: 3.31 Å

EMDB-39526: ASFV RNA polymerase-M1249L complex 19
Method: EM (single particle) / Resolution: 4.04 Å

EMDB-39527: ASFV RNA polymerase-M1249L complex 20
Method: EM (single particle) / Resolution: 3.86 Å

EMDB-39528: ASFV RNA polymerase-M1249L complex 21
Method: EM (single particle) / Resolution: 3.64 Å

EMDB-39529: ASFV RNA polymerase-M1249L complex 24
Method: EM (single particle) / Resolution: 4.04 Å

EMDB-39530: ASFV RNA polymerase-M1249L complex 22
Method: EM (single particle) / Resolution: 4.31 Å

EMDB-39531: ASFV RNA polymerase-M1249L complex 23
Method: EM (single particle) / Resolution: 6.99 Å

EMDB-39536: ASFV RNA polymerase-M1249L complex 25
Method: EM (single particle) / Resolution: 2.94 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

Source
  • african swine fever virus
KeywordsVIRAL PROTEIN / ASFV / RNA polymerase / RNAP

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