XXL-NMR
Financiado
New Routes for the Solution NMR Investigations of Extra Large Biomolecular Assem...
The cell is a collection of dynamic molecular machines. NMR spectroscopy is the method of choice to observe, at atomic resolution, complex conformational changes, transient interactions and dynamics of proteins. Introduction of me...
The cell is a collection of dynamic molecular machines. NMR spectroscopy is the method of choice to observe, at atomic resolution, complex conformational changes, transient interactions and dynamics of proteins. Introduction of methyl specific labelling technology has enabled solution NMR studies of protein assemblies of several hundred kDa. However, this strategy is mostly restricted to symmetrical and thermostable protein assemblies, precluding applications to large medically relevant biological complexes. The increases of linewidths and the high number of signal overlaps hamper the NMR spectra analysis of most hetero-oligomeric large assemblies studied at room temperature. In this project, we will develop two complementary concepts to significantly simplify both NMR spectra and corresponding site specific analysis. We will build a multi-site specific labelling method enabling observation of NMR signals only for the sites of interest in a large protein complex. We will invent a combinatorial strategy to reduce the time required for site-specific identification of each individual NMR signal from a few months to a few hours. New 1H-frequencies edition schemes will be introduced to enhance significantly the NMR spectra’s resolution of very slow tumbling biological particles. These groundbreaking NMR methods will be validated using therapeutic antibodies (150 kDa), ribosome (2.4 MDa) samples, and will be used directly to capture the mechanisms of ATP-fueled human chaperonin (1 MDa) in complex with the aggregation prone form of Huntingtin. This project will provide new technological breakthroughs to push biological applications of NMR significantly beyond its current boundaries. We anticipate that the simplification of the NMR analysis resulting from the new developed NMR routes will transform the solution NMR spectroscopy in a very competitive method to study large medically relevant biomolecular assemblies and molecular machines, so far considered as untargetable.
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Duración del proyecto: 67 meses
Fecha Inicio: 2023-10-27
Fecha Fin: 2029-05-31
Fecha Fin: 2029-05-31
Línea de financiación: concedida
El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-10-27
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2022-ADG:
ERC ADVANCED GRANTS
Cerrada
hace 2 años
Presupuesto
El presupuesto total del proyecto asciende a
3M€
Líder del proyecto
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE...
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5