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DynamicAssemblies

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Conformational studies of highly dynamic viral replication complexes

Paramyxoviruses, including, measles and a number of dangerous human pathogens, are negative strand RNA viruses that express their own machinery for transcription and replication. Different interactions between the nucleoprotein (N... ver más

30/04/2026

CEA

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENER... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Ver 2 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2019-06-11

ERC-2018-ADG: ERC Advanced Grant

I+D

Cerrada hace 6 años

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

2 Participantes

CEA

2.50M€ | Lider

INDUSTRIAS CARNICAS NAVARRAS

268.87K€ | Participante

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Duración del proyecto: 82 meses Fecha Inicio: 2019-06-11
Fecha Fin: 2026-04-30

Líder del proyecto

COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENER... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Paramyxoviruses, including, measles and a number of dangerous human pathogens, are negative strand RNA viruses that express their own machinery for transcription and replication. Different interactions between the nucleoprotein (N) and the phosphoprotein (P) are essential for chaperoning and assembly of N on newly synthesized RNA genomes to form nucleocapsids (NCs), as well as for initiating replication and transcription. Both N and tetrameric P exhibit extensive conformational disorder, with very long, unfolded regions that host important post-translational modification sites as well as regulatory interactions with host and viral partners. The presence of this level of disorder, in viruses whose genetic information is normally so parsimoniously exploited, remains unexplained. The elaboration of time-resolved, atomic resolution descriptions of the interaction trajectories of these highly disordered N:P complexes is extremely challenging, requiring the development of adapted methodologies that can account for their intrinsic flexibility. The role of N and P has been rendered yet more enigmatic following our recent observation that when mixed in solution they form liquid-like droplets. Such membraneless organelles are revolutionizing our understanding of cellular chemical biology, although their physical basis is poorly understood. Our aim is to describe these important complexes at atomic resolution, in particular to understand the role of the extensive conformational dynamics of N and P in the replication cycle. Our recent success in engineering soluble N:P complexes from measles that assemble into NCs, combined with ongoing development of NMR-based methods to investigate the structure, dynamics and interaction kinetics of large, intrinsically disordered proteins, fluorescence spectroscopy, cryoEM, SAXS, crystallography and molecular simulation, will provide the essential tools to investigate the functional mechanisms of these previously inaccessible complexes.

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