Journal article
Structure of the Nipah virus polymerase complex
- Abstract:
- Nipah virus is a highly virulent zoonotic paramyxovirus causing severe respiratory and neurological disease. Despite its lethality, there is no approved treatment for Nipah virus infection. The viral polymerase complex, composed of the polymerase (L) and phosphoprotein (P), replicates and transcribes the viral RNA genome. Here, we describe structures of the Nipah virus L-P polymerase complex and the L-protein’s Connecting Domain (CD). The cryo-electron microscopy L-P complex structure reveals the organization of the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L-protein, and shows how the P-protein, which forms a tetramer, interacts with the RdRp-domain of the L-protein. The crystal structure of the CD-domain alone reveals binding of three Mg ions. Modelling of this domain onto an AlphaFold 3 model of an RNA-L-P complex suggests a catalytic role for one Mg ion in mRNA capping. These findings offer insights into the structural details of the L-P polymerase complex and the molecular interactions between L-protein and P-protein, shedding light on the mechanisms of the replication machinery. This work will underpin efforts to develop antiviral drugs that target the polymerase complex of Nipah virus.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 13.3MB, Terms of use)
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(Supplementary materials, zip, 11.5MB, Terms of use)
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- Publisher copy:
- 10.1038/s44318-024-00321-z
Authors
+ Gates Foundation
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- Funder identifier:
- https://ror.org/0456r8d26
- Grant:
- INV-048922
- Publisher:
- EMBO Press
- Journal:
- EMBO Journal More from this journal
- Volume:
- 44
- Issue:
- 2
- Pages:
- 563-586
- Publication date:
- 2024-12-30
- Acceptance date:
- 2024-11-12
- DOI:
- EISSN:
-
1460-2075
- ISSN:
-
0261-4189
- Language:
-
English
- Keywords:
- Pubs id:
-
2067191
- Local pid:
-
pubs:2067191
- Deposit date:
-
2024-11-27
Terms of use
- Copyright holder:
- Balıkçı et al.
- Copyright date:
- 2024
- Rights statement:
- © 2024 The Author(s). Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/ applies to the data associated with this article, unless otherwise stated in a credit line to the data, but does not extend to the graphical or creative elements of illustrations, charts, or figures. This waiver removes legal barriers to the re-use and mining of research data. According to standard scholarly practice, it is recommended to provide appropriate citation and attribution whenever technically possible.
- Licence:
- CC Attribution (CC BY)
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