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TitleChikungunya virus nonstructural protein 1 is a versatile RNA capping and decapping enzyme.
Journal, issue, pagesJ Biol Chem, Vol. 299, Issue 12, Page 105415, Year 2023
Publish dateOct 31, 2023
AuthorsMichelle Cheok Yien Law / Kuo Zhang / Yaw Bia Tan / Trinh Mai Nguyen / Dahai Luo /
PubMed AbstractChikungunya virus (CHIKV) nonstructural protein 1 (nsP1) contains both the N7-guanine methyltransferase and guanylyltransferase activities and catalyzes the 5' end cap formation of viral RNAs. To ...Chikungunya virus (CHIKV) nonstructural protein 1 (nsP1) contains both the N7-guanine methyltransferase and guanylyltransferase activities and catalyzes the 5' end cap formation of viral RNAs. To further understand its catalytic activity and role in virus-host interaction, we demonstrate that purified recombinant CHIKV nsP1 can reverse the guanylyl transfer reaction and remove the mGMP from a variety of capped RNA substrates including host mRNAs. We then provide the structural basis of this function with a high-resolution cryo-EM structure of nsP1 in complex with the unconventional cap-1 substrate RNA mGpppAU. We show that the 5'ppRNA species generated by decapping can trigger retinoic acid-inducible gene I-mediated interferon response. We further demonstrate that the decapping activity is conserved among the alphaviral nsP1s. To our knowledge, this is a new mechanism through which alphaviruses activate the antiviral immune response. This decapping activity could promote cellular mRNA degradation and facilitate viral gene expression, which is functionally analogous to the cap-snatching mechanism by influenza virus.
External linksJ Biol Chem / PubMed:37918803 / PubMed Central
MethodsEM (single particle)
Resolution2.41 Å
Structure data

EMDB-36159, PDB-8jce:
Cryo-EM Structure of Chikungunya Virus Nonstructural Protein 1 with m7GpppAmU
Method: EM (single particle) / Resolution: 2.41 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-SAH:
S-ADENOSYL-L-HOMOCYSTEINE / S-Adenosyl-L-homocysteine

ChemComp-YG4:
[(2~{R},3~{R},4~{R},5~{R})-5-(6-azanyl-7,8-dihydropurin-9-yl)-2-[[[[[(2~{R},3~{S},4~{R},5~{R})-5-(2-azanyl-7-methyl-6-oxidanylidene-1,8-dihydropurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-oxidanyl-phosphoryl]oxy-oxidanyl-phosphoryl]oxymethyl]-4-methoxy-oxolan-3-yl] [(2~{R},3~{S},4~{R},5~{S})-5-[2,4-bis(oxidanylidene)pyrimidin-1-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methyl hydrogen phosphate

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER / Water

Source
  • chikungunya virus strain s27-african prototype
KeywordsVIRAL PROTEIN / nonstructural protein / Chikungunya virus / RNA cap / replication

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