Nucleocapsid assembly in pneumoviruses is regulated by conformational switching of the N protein
Non-segmented, (-)RNA viruses cause serious human diseases. Human metapneumovirus (HMPV), an emerging pathogen of this order of viruses (Mononegavirales) is one of the main causes of respiratory tract illness in children. To help elucidate the assembly mechanism of the nucleocapsid (the viral RNA ge...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
eLife Sciences Publications
2016
|
| _version_ | 1826311820833456128 |
|---|---|
| author | Renner, M Bertinelli, M Leyrat, C Paesen, G Saraiva de Oliveira, L Huiskonen, JT Grimes, JM |
| author_facet | Renner, M Bertinelli, M Leyrat, C Paesen, G Saraiva de Oliveira, L Huiskonen, JT Grimes, JM |
| author_sort | Renner, M |
| collection | OXFORD |
| description | Non-segmented, (-)RNA viruses cause serious human diseases. Human metapneumovirus (HMPV), an emerging pathogen of this order of viruses (Mononegavirales) is one of the main causes of respiratory tract illness in children. To help elucidate the assembly mechanism of the nucleocapsid (the viral RNA genome packaged by the nucleoprotein N) we present crystallographic structures of HMPV N in its assembled RNA-bound state and in a monomeric state, bound to the polymerase cofactor P. Our structures reveal molecular details of how P inhibits the self-assembly of N and how N transitions between the RNA-free and RNA-bound conformational state. Notably, we observe a role for the C-terminal extension of N in directly preventing premature uptake of RNA by folding into the RNA-binding cleft. Our structures suggest a common mechanism of how the growth of the nucleocapsid is orchestrated, and highlight an interaction site representing an important target for antivirals. |
| first_indexed | 2024-03-07T08:16:55Z |
| format | Journal article |
| id | oxford-uuid:414d88e0-b07a-4f43-abef-bf4ff36aa144 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T08:16:55Z |
| publishDate | 2016 |
| publisher | eLife Sciences Publications |
| record_format | dspace |
| spelling | oxford-uuid:414d88e0-b07a-4f43-abef-bf4ff36aa1442024-01-10T14:33:17ZNucleocapsid assembly in pneumoviruses is regulated by conformational switching of the N proteinJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:414d88e0-b07a-4f43-abef-bf4ff36aa144EnglishSymplectic Elements at OxfordeLife Sciences Publications2016Renner, MBertinelli, MLeyrat, CPaesen, GSaraiva de Oliveira, LHuiskonen, JTGrimes, JMNon-segmented, (-)RNA viruses cause serious human diseases. Human metapneumovirus (HMPV), an emerging pathogen of this order of viruses (Mononegavirales) is one of the main causes of respiratory tract illness in children. To help elucidate the assembly mechanism of the nucleocapsid (the viral RNA genome packaged by the nucleoprotein N) we present crystallographic structures of HMPV N in its assembled RNA-bound state and in a monomeric state, bound to the polymerase cofactor P. Our structures reveal molecular details of how P inhibits the self-assembly of N and how N transitions between the RNA-free and RNA-bound conformational state. Notably, we observe a role for the C-terminal extension of N in directly preventing premature uptake of RNA by folding into the RNA-binding cleft. Our structures suggest a common mechanism of how the growth of the nucleocapsid is orchestrated, and highlight an interaction site representing an important target for antivirals. |
| spellingShingle | Renner, M Bertinelli, M Leyrat, C Paesen, G Saraiva de Oliveira, L Huiskonen, JT Grimes, JM Nucleocapsid assembly in pneumoviruses is regulated by conformational switching of the N protein |
| title | Nucleocapsid assembly in pneumoviruses is regulated by conformational switching of the N protein |
| title_full | Nucleocapsid assembly in pneumoviruses is regulated by conformational switching of the N protein |
| title_fullStr | Nucleocapsid assembly in pneumoviruses is regulated by conformational switching of the N protein |
| title_full_unstemmed | Nucleocapsid assembly in pneumoviruses is regulated by conformational switching of the N protein |
| title_short | Nucleocapsid assembly in pneumoviruses is regulated by conformational switching of the N protein |
| title_sort | nucleocapsid assembly in pneumoviruses is regulated by conformational switching of the n protein |
| work_keys_str_mv | AT rennerm nucleocapsidassemblyinpneumovirusesisregulatedbyconformationalswitchingofthenprotein AT bertinellim nucleocapsidassemblyinpneumovirusesisregulatedbyconformationalswitchingofthenprotein AT leyratc nucleocapsidassemblyinpneumovirusesisregulatedbyconformationalswitchingofthenprotein AT paeseng nucleocapsidassemblyinpneumovirusesisregulatedbyconformationalswitchingofthenprotein AT saraivadeoliveiral nucleocapsidassemblyinpneumovirusesisregulatedbyconformationalswitchingofthenprotein AT huiskonenjt nucleocapsidassemblyinpneumovirusesisregulatedbyconformationalswitchingofthenprotein AT grimesjm nucleocapsidassemblyinpneumovirusesisregulatedbyconformationalswitchingofthenprotein |