Correlation Engine 2.0
Clear Search sequence regions


Sizes of these terms reflect their relevance to your search.

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 show 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 is 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.

Citation

Helder Veras Ribeiro-Filho, Gabriel Ernesto Jara, Fernanda Aparecida Heleno Batista, Gabriel Ravanhani Schleder, Celisa Caldana Costa Tonoli, Adriana Santos Soprano, Samuel Leite GuimarĂ£es, Antonio Carlos Borges, Alexandre Cassago, Marcio Chaim Bajgelman, Rafael Elias Marques, Daniela Barretto Barbosa Trivella, Kleber Gomes Franchini, Ana Carolina Migliorini Figueira, Celso Eduardo Benedetti, Paulo Sergio Lopes-de-Oliveira. Structural dynamics of SARS-CoV-2 nucleocapsid protein induced by RNA binding. PLoS computational biology. 2022 May;18(5):e1010121

Expand section icon Mesh Tags

Expand section icon Substances


PMID: 35551296

View Full Text