Artículo
Molten Globule Driven and Self-downmodulated Phase Separation of a Viral Factory Scaffold: Phase separation of a viral replication scaffold
Salgueiro, Mariano
; Camporeale, Gabriela
; Visentin, Araceli Natalia
; Aran, Martin
; Pellizza Pena, Leonardo Agustín
; Esperante, Sebastian
; Corbat, Agustín Andrés
; Grecco, Hernan Edgardo
; Sousa, Belén; Esperón, Ramiro; Borkosky, Silvia Susana
; de Prat Gay, Gonzalo
Fecha de publicación:
08/2023
Editorial:
Academic Press Ltd - Elsevier Science Ltd
Revista:
Journal of Molecular Biology
ISSN:
0022-2836
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Viral factories of liquid-like nature serve as sites for transcription and replication in most viruses. The respiratory syncytial virus factories include replication proteins, brought together by the phosphoprotein (P) RNA polymerase cofactor, present across non-segmented negative stranded RNA viruses. Homotypic liquid–liquid phase separation of RSV-P is governed by an α-helical molten globule domain, and strongly self-downmodulated by adjacent sequences. Condensation of P with the nucleoprotein N is stoichiometrically tuned, defining aggregate-droplet and droplet-dissolution boundaries. Time course analysis show small N-P nuclei gradually coalescing into large granules in transfected cells. This behavior is recapitulated in infection, with small puncta evolving to large viral factories, strongly suggesting that P-N nucleation-condensation sequentially drives viral factories. Thus, the tendency of P to undergo phase separation is moderate and latent in the full-length protein but unleashed in the presence of N or when neighboring disordered sequences are deleted. This, together with its capacity to rescue nucleoprotein-RNA aggregates suggests a role as a “solvent-protein”.
Palabras clave:
LLPS
,
MOLTEN GLOBULE
,
PHOSPHOPROTEIN
,
RSV
,
VIRAL FACTORY
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(IFIBA)
Articulos de INST.DE FISICA DE BUENOS AIRES
Articulos de INST.DE FISICA DE BUENOS AIRES
Articulos(IIBBA)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Articulos de INST.DE INVEST.BIOQUIMICAS DE BS.AS(I)
Citación
Salgueiro, Mariano; Camporeale, Gabriela; Visentin, Araceli Natalia; Aran, Martin; Pellizza Pena, Leonardo Agustín; et al.; Molten Globule Driven and Self-downmodulated Phase Separation of a Viral Factory Scaffold: Phase separation of a viral replication scaffold; Academic Press Ltd - Elsevier Science Ltd; Journal of Molecular Biology; 435; 16; 8-2023; 1-18
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