Molten Globule Driven and Self-downmodulated Phase Separation of a Viral Factory Scaffold.

Autor: Salgueiro M; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA) CONICET, Buenos Aires, Argentina., Camporeale G; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA) CONICET, Buenos Aires, Argentina., Visentin A; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA) CONICET, Buenos Aires, Argentina., Aran M; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA) CONICET, Buenos Aires, Argentina., Pellizza L; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA) CONICET, Buenos Aires, Argentina., Esperante SA; Fundación Infant and CONICET, Buenos Aires, Argentina., Corbat A; Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires, and IFIBA, CONICET, Buenos Aires, Argentina., Grecco H; Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires, and IFIBA, CONICET, Buenos Aires, Argentina., Sousa B; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA) CONICET, Buenos Aires, Argentina., Esperón R; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA) CONICET, Buenos Aires, Argentina., Borkosky SS; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA) CONICET, Buenos Aires, Argentina., de Prat-Gay G; Fundación Instituto Leloir, Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA) CONICET, Buenos Aires, Argentina. Electronic address: gpg@leloir.org.ar.
Jazyk: angličtina
Zdroj: Journal of molecular biology [J Mol Biol] 2023 Aug 15; Vol. 435 (16), pp. 168153. Date of Electronic Publication: 2023 May 18.
DOI: 10.1016/j.jmb.2023.168153
Abstrakt: 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".
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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