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TitleHigher-order structures of the foot-and-mouth disease virus RNA-dependent RNA polymerase required for genome replication.
Journal, issue, pagesCommun Biol, Vol. 5, Issue 1, Page 61, Year 2022
Publish dateJan 17, 2022
AuthorsEleni-Anna Loundras / James Streetley / Morgan R Herod / Rebecca Thompson / Mark Harris / David Bhella / Nicola J Stonehouse /
PubMed AbstractReplication of many positive-sense RNA viruses occurs within intracellular membrane-associated compartments. These are thought to provide a favourable environment for replication to occur, ...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 3D), 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 3D complexes as a dynamic scaffold within which RNA replication can occur.
External linksCommun Biol / PubMed:35039618 / PubMed Central
MethodsEM (helical sym.)
Resolution7.3 - 9.5 Å
Structure data

EMDB-12093:
Higher-order structures of the foot-and-mouth disease virus RNA-dependent RNA polymerase required for dynamic inter-molecular interactions involved in viral genome replication
Method: EM (helical sym.) / Resolution: 7.3 Å

EMDB-12094:
Higher-order structures of the foot-and-mouth disease virus RNA-dependent RNA polymerase required for dynamic inter-molecular interactions involved in viral genome replication
Method: EM (helical sym.) / Resolution: 9.5 Å

EMDB-12096:
Higher-order structures of the foot-and-mouth disease virus RNA-dependent RNA polymerase required for dynamic inter-molecular interactions involved in viral genome replication
Method: EM (helical sym.) / Resolution: 8.5 Å

EMDB-12097:
Higher-order structures of the foot-and-mouth disease virus RNA-dependent RNA polymerase required for dynamic inter-molecular interactions involved in viral genome replication
Method: EM (helical sym.) / Resolution: 7.7 Å

EMDB-12098:
Higher-order structures of the foot-and-mouth disease virus RNA-dependent RNA polymerase required for dynamic inter-molecular interactions involved in viral genome replication
Method: EM (helical sym.) / Resolution: 7.6 Å

EMDB-12099:
Higher-order structures of the foot-and-mouth disease virus RNA-dependent RNA polymerase required for dynamic inter-molecular interactions involved in viral genome replication
Method: EM (helical sym.) / Resolution: 7.6 Å

EMDB-12100:
Higher-order structures of the foot-and-mouth disease virus RNA-dependent RNA polymerase required for dynamic inter-molecular interactions involved in viral genome replication
Method: EM (helical sym.) / Resolution: 7.3 Å

EMDB-12101:
Higher-order structures of the foot-and-mouth disease virus RNA-dependent RNA polymerase required for dynamic inter-molecular interactions involved in viral genome replication
Method: EM (helical sym.) / Resolution: 7.5 Å

EMDB-12102:
Higher-order structures of the foot-and-mouth disease virus RNA-dependent RNA polymerase required for dynamic inter-molecular interactions involved in viral genome replication
Method: EM (helical sym.) / Resolution: 7.3 Å

Source
  • Foot-and-mouth disease virus

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