Self-capping of nucleoprotein filaments protects Newcastle Disease Virus genome
Abstract
Non-segmented negative-strand RNA viruses, such as Measles, Ebola and Newcastle disease viruses (NDV), encapsidate viral genomic RNAs into helical nucleocapsids which serve as the template for viral replication and transcription. Here, the clam-shaped nucleocapsid structure, where the NDV viral genome is sequestered, was determined at 4.8 Å resolution by cryo-electron microscopy. The clam-shaped structure is composed of two single-turn spirals packed in a back-to-back mode, and the tightly packed structure functions as a seed for nucleocapsid to assemble from both directions and grows into double-headed filaments with two separate RNA strings inside. Disruption of this structure by mutations on its loop interface yielded a single-headed unfunctional filament.
Data availability
The cryo-EM density map has been deposited in EMDB with the accession number EMD-9793. The atom coordinates of the structure have been deposited in PDB with the PDB ID 6JC3.
-
The Cryo-EM structure of nucleoprotein-RNA complex of Newcastle disease virusRCSB Protein Data Bank, 6JC3.
-
The Cryo-EM structure of nucleoprotein-RNA complex of Newcastle disease virusElectron Microscopy Data Bank, EMD-9793.
Article and author information
Author details
Funding
National Nature Science Foundation of China grant (31330019)
- Zhi-Jie Liu
National Nature Science Foundation of China grant (31770948)
- Songying Ouyang
National Nature Science Foundation of China grant (31570875)
- Songying Ouyang
National Natural Science Foundation of China grant (81590761)
- Songying Ouyang
the National Key R&D program of China (2017YFA0504800)
- Qing-Tao Shen
Yunnan Provincial Science and Technology Department Project (2016FC007)
- Zhi-Jie Liu
The Pujiang Talent program (17PJ1406700)
- Qing-Tao Shen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Song et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,022
- views
-
- 309
- downloads
-
- 22
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Immunology and Inflammation
- Microbiology and Infectious Disease
Circulating sexual stages of Plasmodium falciparum (Pf) can be transmitted from humans to mosquitoes, thereby furthering the spread of malaria in the population. It is well established that antibodies can efficiently block parasite transmission. In search for naturally acquired antibodies targets on sexual stages, we established an efficient method for target-agnostic single B cell activation followed by high-throughput selection of human monoclonal antibodies (mAbs) reactive to sexual stages of Pf in the form of gametes and gametocyte extracts. We isolated mAbs reactive against a range of Pf proteins including well-established targets Pfs48/45 and Pfs230. One mAb, B1E11K, was cross-reactive to various proteins containing glutamate-rich repetitive elements expressed at different stages of the parasite life cycle. A crystal structure of two B1E11K Fab domains in complex with its main antigen, RESA, expressed on asexual blood stages, showed binding of B1E11K to a repeating epitope motif in a head-to-head conformation engaging in affinity-matured homotypic interactions. Thus, this mode of recognition of Pf proteins, previously described only for Pf circumsporozoite protein (PfCSP), extends to other repeats expressed across various stages. The findings augment our understanding of immune-pathogen interactions to repeating elements of the Plasmodium parasite proteome and underscore the potential of the novel mAb identification method used to provide new insights into the natural humoral immune response against Pf.
-
- Microbiology and Infectious Disease
The type VI secretion system (T6SS) is a sophisticated, contact-dependent nanomachine involved in interbacterial competition. To function effectively, the T6SS must penetrate the membranes of both attacker and target bacteria. Structures associated with the cell envelope, like polysaccharides chains, can therefore introduce spatial separation and steric hindrance, potentially affecting the efficacy of the T6SS. In this study, we examined how the capsular polysaccharide (CPS) of Acinetobacter baumannii affects T6SS’s antibacterial function. Our findings show that the CPS confers resistance against T6SS-mediated assaults from rival bacteria. Notably, under typical growth conditions, the presence of the surface-bound capsule also reduces the efficacy of the bacterium’s own T6SS. This T6SS impairment is further enhanced when CPS is overproduced due to genetic modifications or antibiotic treatment. Furthermore, we demonstrate that the bacterium adjusts the level of the T6SS inner tube protein Hcp according to its secretion capacity, by initiating a degradation process involving the ClpXP protease. Collectively, our findings contribute to a better understanding of the dynamic relationship between T6SS and CPS and how they respond swiftly to environmental challenges.