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-Structure paper
Title | Chikungunya virus nonstructural protein 1 is a versatile RNA capping and decapping enzyme. |
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Journal, issue, pages | J Biol Chem, Vol. 299, Issue 12, Page 105415, Year 2023 |
Publish date | Oct 31, 2023 |
Authors | Michelle Cheok Yien Law / Kuo Zhang / Yaw Bia Tan / Trinh Mai Nguyen / Dahai Luo / |
PubMed Abstract | 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 ...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 links | J Biol Chem / PubMed:37918803 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.41 Å |
Structure data | EMDB-36159, PDB-8jce: |
Chemicals | ChemComp-ZN: ChemComp-SAH: ChemComp-YG4: ChemComp-MG: ChemComp-HOH: |
Source |
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Keywords | VIRAL PROTEIN / nonstructural protein / Chikungunya virus / RNA cap / replication |