Structural Insights into Bunyavirus Replication and Its Regulation by the vRNA Promoter
| Autor: | Stephen Cusack, Hélène Malet, Piotr Gerlach, Juan Reguera |
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| Přispěvatelé: | European Molecular Biology Laboratory [Heidelberg] (EMBL), Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF), European Molecular Biology Laboratory [Grenoble] (EMBL), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2015 |
| Předmět: |
Models
Molecular Orthobunyavirus viruses MESH: Sequence Alignment MESH: Catalytic Domain MESH: Orthobunyavirus RNA-dependent RNA polymerase Sequence alignment MESH: Amino Acid Sequence Crystallography X-Ray Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Catalytic Domain MESH: Promoter Regions Genetic Amino Acid Sequence Promoter Regions Genetic Peptide sequence Polymerase 030304 developmental biology Genetics 0303 health sciences [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] biology 030306 microbiology Biochemistry Genetics and Molecular Biology(all) Ribonucleoprotein particle RNA RNA virus MESH: Crystallography X-Ray RNA-Dependent RNA Polymerase biology.organism_classification 3. Good health MESH: Ribonucleoproteins [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] Ribonucleoproteins MESH: RNA Viral biology.protein RNA Viral MESH: RNA Replicase Sequence Alignment MESH: Models Molecular |
| Zdroj: | Cell Cell, Elsevier, 2015, 161 (6), pp.1267-1279. ⟨10.1016/j.cell.2015.05.006⟩ Cell, 2015, 161 (6), pp.1267-1279. ⟨10.1016/j.cell.2015.05.006⟩ |
| ISSN: | 0092-8674 1097-4172 |
| DOI: | 10.1016/j.cell.2015.05.006 |
| Popis: | Summary Segmented negative-strand RNA virus (sNSV) polymerases transcribe and replicate the viral RNA (vRNA) within a ribonucleoprotein particle (RNP). We present cryo-EM and X-ray structures of, respectively, apo- and vRNA bound La Crosse orthobunyavirus (LACV) polymerase that give atomic-resolution insight into how such RNPs perform RNA synthesis. The complementary 3′ and 5′ vRNA extremities are sequence specifically bound in separate sites on the polymerase. The 5′ end binds as a stem-loop, allosterically structuring functionally important polymerase active site loops. Identification of distinct template and product exit tunnels allows proposal of a detailed model for template-directed replication with minimal disruption to the circularised RNP. The similar overall architecture and vRNA binding of monomeric LACV to heterotrimeric influenza polymerase, despite high sequence divergence, suggests that all sNSV polymerases have a common evolutionary origin and mechanism of RNA synthesis. These results will aid development of replication inhibitors of diverse, serious human pathogenic viruses. Graphical Abstract Highlights • Bunyavirus polymerase binds its complementary 3′ and 5′ vRNA ends in distinct sites • 5′ vRNA binding allosterically structures and activates the polymerase catalytic site • Distinct template/product exit tunnels explain RNA synthesis in a circularized RNP • Monomeric bunyavirus and trimeric influenza polymerases are structurally similar The structure of the monomeric bunyavirus polymerase reveals that divergent segmented negative-strand RNA virus polymerases have a common overall architecture, explains how viral RNA binding allosterically regulates polymerase activity, and suggests a replication model that could apply to all related RNA viruses. |
| Databáze: | OpenAIRE |
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