RNA Therapeutics Institute
Amino Acids, Peptides, and Proteins | Biochemistry, Biophysics, and Structural Biology | Enzymes and Coenzymes | Nucleic Acids, Nucleotides, and Nucleosides | Virology | Virus Diseases | Viruses
The large (L) proteins of non-segmented, negative-strand RNA viruses are multifunctional enzymes that produce capped, methylated, and polyadenylated mRNA and replicate the viral genome. A phosphoprotein (P), required for efficient RNA-dependent RNA polymerization from the viral ribonucleoprotein (RNP) template, regulates the function and conformation of the L protein. We report the structure of vesicular stomatitis virus L in complex with its P cofactor determined by electron cryomicroscopy at 3.0 A resolution, enabling us to visualize bound segments of P. The contacts of three P segments with multiple L domains show how P induces a closed, compact, initiation-competent conformation. Binding of P to L positions its N-terminal domain adjacent to a putative RNA exit channel for efficient encapsidation of newly synthesized genomes with the nucleoprotein and orients its C-terminal domain to interact with an RNP template. The model shows that a conserved tryptophan in the priming loop can support the initiating 5' nucleotide.
antiviral, ebola, polymerase, rabies, respiratory syncytial virus, rhabdoviruses
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Copyright 2019 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
Jenni S, Bloyet LM, Diaz-Avalos R, Liang B, Whelan SPJ, Grigorieff N, Harrison SC. Structure of the Vesicular Stomatitis Virus L Protein in Complex with Its Phosphoprotein Cofactor. Cell Rep. 2020 Jan 7;30(1):53-60.e5. doi: 10.1016/j.celrep.2019.12.024. PMID: 31914397. Link to article on publisher's site
Jenni S, Bloyet L, Diaz-Avalos R, Liang B, Whelan SP, Grigorieff N, Harrison SC. (2020). Structure of the Vesicular Stomatitis Virus L Protein in Complex with Its Phosphoprotein Cofactor. Open Access Articles. https://doi.org/10.1016/j.celrep.2019.12.024. Retrieved from https://escholarship.umassmed.edu/oapubs/4110
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