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Two-Field Nuclear Magnetic Resonance Spectroscopy for the Exploration of Biomolecular Dynamics

Two-Field Nuclear Magnetic Resonance Spectroscopy for the Exploration of Biomolecular Dynamics

Objective

The paradigm of the structure-function relationship in proteins is outdated. Biological macromolecules and supramolecular assemblies are highly dynamic objects. Evidence that their motions are of utmost importance to their functions is regularly identified. The understanding of the physical chemistry of biological processes at an atomic level has to rely not only on the description of structure but also on the characterization of molecular motions.
The investigation of protein motions will be undertaken with a very innovative methodological approach in nuclear magnetic resonance relaxation. In order to widen the ranges of frequencies at which local motions in proteins are probed, we will first use and develop new techniques for a prototype shuttle system for the measurement of relaxation at low fields on a high-field NMR spectrometer. Second, we will develop a novel system: a set of low-field NMR spectrometers designed as accessories for high-field spectrometers. Used in conjunction with the shuttle, this system will offer (i) the sensitivity and resolution (i.e. atomic level information) of a high-field spectrometer (ii) the access to low fields of a relaxometer and (iii) the ability to measure a wide variety of relaxation rates with high accuracy. This system will benefit from the latest technology in homogeneous permanent magnet development to allow a control of spin systems identical to that of a high-resolution probe. This new apparatus will open the way to the use of NMR relaxation at low fields for the refinement of protein motions at an atomic scale.
Applications of this novel approach will focus on the bright side of protein dynamics: (i) the largely unexplored dynamics of intrinsically disordered proteins, and (ii) domain motions in large proteins. In both cases, we will investigate a series of diverse protein systems with implications in development, cancer and immunity.

Principal Investigator

Fabien Ferrage (Dr.)

Host institution

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

Address

Rue Michel Ange 3
75794 Paris

France

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 462 080

Principal Investigator

Fabien Ferrage (Dr.)

Administrative Contact

Julie Zittel (Ms.)

Beneficiaries (1)

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CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

France

EU Contribution

€ 1 462 080

Project information

Grant agreement ID: 279519

Status

Closed project

  • Start date

    1 January 2012

  • End date

    31 December 2017

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 1 462 080

  • EU contribution

    € 1 462 080

Hosted by:

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

France