Details

Autor(en) / Beteiligte

• Ribeiro-Filho, Helder Veras
• Jara, Gabriel Ernesto
• Batista, Fernanda Aparecida Heleno
• Schleder, Gabriel Ravanhani
• Costa Tonoli, Celisa Caldana
• Soprano, Adriana Santos
• Guimarães, Samuel Leite
• Borges, Antonio Carlos
• Cassago, Alexandre
• Bajgelman, Marcio Chaim
• Marques, Rafael Elias
• Trivella, Daniela Barretto Barbosa
• Franchini, Kleber Gomes
• Figueira, Ana Carolina Migliorini
• Benedetti, Celso Eduardo
• Lopes-de-Oliveira, Paulo Sergio
• Onufriev, Alexey

Titel

Structural dynamics of SARS-CoV-2 nucleocapsid protein induced by RNA binding

Ist Teil von

• PLoS computational biology, 2022-05, Vol.18 (5), p.e1010121-e1010121

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.