8JCE

Cryo-EM Structure of Chikungunya Virus Nonstructural Protein 1 with m7GpppAmU

Summary for 8JCE

• Entry DOI: 10.2210/pdb8jce/pdb
• EMDB information: 36159
• Descriptor: mRNA-capping enzyme nsP1, ZINC ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (6 entities in total)
• Functional Keywords: nonstructural protein, chikungunya virus, rna cap, replication, viral protein
• Biological source: Chikungunya virus strain S27-African prototype
• Total number of polymer chains: 12
• Total formula weight: 762891.11

Authors

Zhang, K.,Law, M.C.Y.,Nguyen, T.M.,Tan, Y.B.,Wirawan, M.,Law, Y.S.,Luo, D.H. (deposition date: 2023-05-11, release date: 2023-11-15, Last modification date: 2025-06-18)

Primary citation

Law, M.C.Y.,Zhang, K.,Tan, Y.B.,Nguyen, T.M.,Luo, D.
Chikungunya virus nonstructural protein 1 is a versatile RNA capping and decapping enzyme.
J.Biol.Chem., 299:105415-105415, 2023

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 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.

PubMed: 37918803
DOI: 10.1016/j.jbc.2023.105415

Experimental method

ELECTRON MICROSCOPY (2.41 Å)