UMMS Affiliation

RNA Therapeutics Institute

Publication Date

2020-01-07

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Biochemistry, Biophysics, and Structural Biology | Enzymes and Coenzymes | Nucleic Acids, Nucleotides, and Nucleosides | Virology | Virus Diseases | Viruses

Abstract

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.

Keywords

antiviral, ebola, polymerase, rabies, respiratory syncytial virus, rhabdoviruses

Rights and Permissions

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

10.1016/j.celrep.2019.12.024

Source

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

Journal/Book/Conference Title

Cell reports

Related Resources

Link to Article in PubMed

PubMed ID

31914397

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Share

COinS