DynamicAssemblies
Financiado
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...
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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Duración del proyecto: 82 meses
Fecha Inicio: 2019-06-11
Fecha Fin: 2026-04-30
Fecha Fin: 2026-04-30
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2019-06-11
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2018-ADG:
ERC Advanced Grant
Cerrada
hace 6 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENER...
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Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
268.87K€ |
Participante