CryoEM structure of the Nipah virus nucleocapsid assembly
| Autor: | Alfred A. Antson, Sandra J. Greive, Huw T. Jenkins, De-Sheng Ker |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular RNA viruses Protein Structure Comparison Molecular biology Nipah virus viruses Molecular Conformation Filoviridae RNA-binding proteins Protomer medicine.disease_cause Pathology and Laboratory Medicine Genome Nucleocapsids Biochemistry 0302 clinical medicine Protein structure Atomic resolution Medicine and Health Sciences Nucleotide Biology (General) RNA structure chemistry.chemical_classification 0303 health sciences biology Nucleocapsid Proteins 3. Good health Nucleic acids Medical Microbiology Viral Pathogens Viruses RNA Viral Pathogens Henipavirus Research Article Protein Structure Paramyxoviridae QH301-705.5 Highly pathogenic Immunology Viral Structure Microbiology 03 medical and health sciences Virology Genetics medicine Nucleic acid structure Nucleocapsid Protein Interactions Microbial Pathogens 030304 developmental biology Ebola virus 030306 microbiology Cryoelectron Microscopy Nipah Virus Organisms RNA Biology and Life Sciences Proteins RNA virus RC581-607 biology.organism_classification Macromolecular structure analysis chemistry Paramyxoviruses Parasitology Immunologic diseases. Allergy 030217 neurology & neurosurgery |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Vol 17, Iss 7, p e1009740 (2021) |
| ISSN: | 1553-7366 |
| DOI: | 10.1101/2020.01.20.912261 |
| Popis: | Nipah and its close relative Hendra are highly pathogenic zoonotic viruses, storing their ssRNA genome in a helical nucleocapsid assembly formed by the N protein, a major viral immunogen. Here, we report the first cryoEM structure for a Henipavirus RNA-bound nucleocapsid assembly, at 3.5 Å resolution. The helical assembly is stabilised by previously undefined N- and C-terminal segments, contributing to subunit-subunit interactions. RNA is wrapped around the nucleocapsid protein assembly with a periodicity of six nucleotides per protomer, in the “3-bases-in, 3-bases-out” conformation, with protein plasticity enabling non-sequence specific interactions. The structure reveals commonalities in RNA binding pockets and in the conformation of bound RNA, not only with members of the Paramyxoviridae family, but also with the evolutionarily distant Filoviridae Ebola virus. Significant structural differences with other Paramyxoviridae members are also observed, particularly in the position and length of the exposed α-helix, residues 123–139, which may serve as a valuable epitope for surveillance and diagnostics. Author summary Nipah virus is a highly pathogenic RNA virus which, along with the closely related Hendra virus, emerged relatively recently. Due to ~40% mortality rate and evidence of animal-to-human as well as human-to-human transmission, development of antivirals against the Nipah and henipaviral disease is particularly urgent. In common with other single-stranded RNA viruses, including Ebola and coronaviruses, the nucleocapsid assembly of the Nipah virus safeguards the viral genome, protecting it from degradation and facilitating its encapsidation and storage inside the virion. Here, we used cryo-electron microscopy to determine accurate three-dimensional structure for several different assemblies of the Nipah virus nucleocapsid protein, in particular a detailed structure for the complex of this protein with RNA. This structural information is important for understanding detailed molecular interactions driving and stabilizing the nucleocapsid assembly formation that are of fundamental importance for understanding similar processes in a large group of ssRNA viruses. Apart from highlighting structural similarities and differences with nucleocapsid proteins of other viruses of the Paramyxoviridae family, these data will inform the development of new antiviral approaches for the henipaviruses. |
| Databáze: | OpenAIRE |
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