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Structure of paramagnetic integral membrane metalloproteins by MAS-NMR

Objective

Integral membrane metalloproteins are involved in the transport and homeostasis of metal ions, as well as in key redox reactions that have a tremendous impact on many fields within life sciences, environment, energy, and industry.
Most of our understanding of fine details of biochemical processes derives from atomic or molecular structures obtained by diffraction methods on single crystal samples. However, in the case of integral membrane systems, single crystals large enough for X-ray diffraction cannot be easily obtained, and the problem of structure elucidation is largely unsolved.
We have recently pioneered a breakthrough approach using Magic-Angle Spinning Nuclear Magnetic Resonance (MAS-NMR) for the atomic-level characterization of paramagnetic materials and complex biological macromolecules. The proposed project aims to leverage these new advances through a series of new concepts i) to improve the resolution and sensitivity of MAS-NMR from nuclei surrounding a paramagnetic metal ion, such as e.g. cobalt, nickel and iron, and ii) to extend its applicability to large integral membrane proteins in lipid membrane environments. With these methods, we will enable the determination of structure-activity relationships in integral membrane metalloenzymes and transporters, by combining the calculation of global structure and dynamics with measurement of the electronic features of metal ions.
These goals require a leap forward with respect to today’s protocols, and we propose to achieve this through a combination of innovative NMR experiments and isotopic labeling, faster MAS rates and high magnetic fields. As outlined here, the approaches go well beyond the frontier of current research. The project will yield a broadly applicable method for the structural characterization of essential cellular processes and thereby will provide a powerful tool to solve challenges at the forefront of molecular and chemical sciences today.

Field of science

  • /natural sciences/chemical sciences/analytical chemistry/spectroscopy
  • /social sciences/social and economic geography/transport
  • /medical and health sciences/basic medicine/physiology/homeostasis
  • /natural sciences/chemical sciences/electrochemistry/electrolysis
  • /natural sciences/chemical sciences/inorganic chemistry/metals
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins
  • /natural sciences/biological sciences/biochemistry/biomolecules/lipids

Call for proposal

ERC-2014-CoG
See other projects for this call

Funding Scheme

ERC-COG - Consolidator Grant

Host institution

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Address
Rue Michel Ange 3
75794 Paris
France
Activity type
Research Organisations
EU contribution
€ 2 499 375

Beneficiaries (1)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France
EU contribution
€ 2 499 375
Address
Rue Michel Ange 3
75794 Paris
Activity type
Research Organisations