Loundras, E.-A., Streetley, J. , Herod, M. R., Thompson, R., Harris, M., Bhella, D. and Stonehouse, N. J. (2022) Higher-order structures of the foot-and-mouth disease virus RNA-dependent RNA polymerase required for genome replication. Communications Biology, 5, 61. (doi: 10.1038/s42003-021-02989-z) (PMID:35039618) (PMCID:PMC8764057)
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Publisher's URL: https://www.nature.com/articles/s42003-021-02989-z
Abstract
Replication of many positive-sense RNA viruses occurs within intracellular membrane-associated compartments. These are thought to provide a favourable environment for replication to occur, concentrating essential viral structural and nonstructural components, as well as protecting these components from host-cell pathogen recognition and innate immune responses. However, the details of the molecular interactions and dynamics within these structures is very limited. One of the key components of the replication machinery is the RNA-dependent RNA polymerase, RdRp. This enzyme has been shown to form higher-order fibrils in vitro. Here, using the RdRp from foot-and-mouth disease virus (termed 3Dpol), we report fibril structures, solved at ~7-9 Å resolution by cryo-EM, revealing multiple conformations of a flexible assembly. Fitting high-resolution coordinates led to the definition of potential intermolecular interactions. We employed mutagenesis using a sub-genomic replicon system to probe the importance of these interactions for replication. We use these data to propose models for the role of higher-order 3Dpol complexes as a dynamic scaffold within which RNA replication can occur.
| Item Type: | Articles |
|---|---|
| Additional Information: | E.A.L. and M.R.H. were funded by the BBSRC (grants BB/F01614X/1, BB/K003801/1 and BB/P001459/1). M.R.H. was also funded by a Medical Research Council CDA (MR/S007229/1). The Astbury Biostructure laboratory was funded by the University of Leeds and the Wellcome Trust (108466/Z/15/Z). M.H. was funded by a Wellcome Investigator Award (grant number 096670/Z/11/Z). D.B. was funded by the UK Medical Research Council (MC_UU_12014/7) J.S was funded by the UK Medical Research Council (MR/M000451/1). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Streetley, Dr James and Bhella, Professor David |
| Authors: | Loundras, E.-A., Streetley, J., Herod, M. R., Thompson, R., Harris, M., Bhella, D., and Stonehouse, N. J. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Communications Biology |
| Publisher: | Nature Research |
| ISSN: | 2399-3642 |
| ISSN (Online): | 2399-3642 |
| Copyright Holders: | Copyright © 2022 The Authors |
| First Published: | First published in Communications Biology 5: 61 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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