NMR and lipids - proteins interactions
Membrane proteins account for about 30 % of the expressed protein and are major target for therapeutic drugs but very few 3D structures are known so far, due to weakness of analysis methods for such system. The same limitations occur for studying lipids – proteins interactions either for integral membrane proteins, or for peripheral membrane proteins which very often bind membrane in a reversible way.
Our objectives are to underline and characterize interactions of peripheral membrane proteins with lipids. Specificity of interactions according to the nature of lipids and the structure of systems and structural modifications of the proteins will be determined by complementary approach such as fluorescence, circular dichroïsm and NMR.
Themes currently studied
- Dystrophin is the protein which absence causes Duchenne muscular dystrophy. In case of Becker muscular dystrophy, mutations of the central rod domain are associated with more or less severe phenotypes. The hypothesis to test is that this diversity in the severity of phenotype is related to modifications either of stability or conformation of proteins, or of interactions with lipids; these modifications being variable according to mutations. More about this...
- Structural changes of liposomes associated cytochrome c may be studied by dissociation dynamic of the cytochrome c – lipids complexes by using paramagnetic NMR. The objective will be especially to work with fragments of mitochondrial internal membrane to mimic cell situation.
- We have shown recently that the dissociation kinetic constant of molecules interacting with phospholipids was sufficient for allowing utilization of small unilamellar vesicules (SUV) and proton NMR in conditions of liquid NMR. More about this ...This observation opens real interesting possibilities for structural analysis of bioactive peptides in dynamic association with membranes. Collaboration is going on with M. Baudy-Floc'h (UMR CNRS 6510,
) about structural determination of biologically active hydrazinopeptoïdes. More about this ... Rennes, France