Structural dynamics of SARS-CoV-2 nucleocapsid protein induced by RNA binding
| Autor: | Celisa Caldana Costa Tonoli, Kleber G. Franchini, Marcio C. Bajgelman, Gabriel Ernesto Jara, Celso Eduardo Benedetti, Antonio Carlos Borges, Ana Carolina Migliorini Figueira, Adriana Santos Soprano, Gabriel Ravanhani Schleder, Fernanda Aparecida Heleno Batista, Helder Veras Ribeiro-Filho, Alexandre Cassago, Samuel Leite Guimarães, Rafael Elias Marques, Paulo Sérgio Lopes-de-Oliveira, Daniela Barrreto Barbosa Trivella |
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| Rok vydání: | 2022 |
| Předmět: |
Molecular model
Molecular Dynamics Simulation Virus Molecular dynamics Cellular and Molecular Neuroscience Viral life cycle Transcription (biology) Genetics Coronavirus Nucleocapsid Proteins Humans Molecular Biology Ecology Evolution Behavior and Systematics Ecology Chemistry SARS-CoV-2 RNA COVID-19 Nucleocapsid Proteins Phosphoproteins Microscopy Electron Computational Theory and Mathematics Phosphoprotein Modeling and Simulation Biophysics RNA Viral CTD Protein Binding |
| Zdroj: | PLoS computational biology. 18(5) |
| ISSN: | 1553-7358 |
| Popis: | The nucleocapsid (N) protein of the SARS-CoV-2 virus, the causal agent of COVID-19, is a multifunction phosphoprotein that plays critical roles in the virus life cycle, including transcription and packaging of the viral RNA. To play such diverse roles, the N protein has two globular RNA-binding modules, the N-(NTD) and C-terminal (CTD) domains, which are connected by an intrinsically disordered region. Despite the wealth of structural data available for the isolated NTD and CTD, how these domains are arranged in the full-length protein and how the oligomerization of N influences its RNA-binding activity remains largely unclear. Herein, using experimental data from electron microscopy and biochemical/biophysical techniques combined with molecular modeling and molecular dynamics simulations, we showed that, in the absence of RNA, the N protein formed structurally dynamic dimers, with the NTD and CTD arranged in extended conformations. However, in the presence of RNA, the N protein assumed a more compact conformation where the NTD and CTD are packed together. We also provided an octameric model for the full-length N bound to RNA that was consistent with electron microscopy images of the N protein in the presence of RNA. Together, our results shed new light on the dynamics and higher-order oligomeric structure of this versatile protein. |
| Databáze: | OpenAIRE |
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