NMR of Membranes and Protein Assemblies

Our research focuses on structural biology and biophysics of biological assemblies, ranging from pathological and functional amyloids to membrane proteins, cell wall and lipid membranes. We develop and mainly apply magic-angle spinning and static wide line solid-state NMR and EPR spectroscopies to capture structural and dynamic details of biomolecules at atomic resolution.
Our group manages the NMR facility of the CBMN @ IECB (https://www.iecb.u-bordeaux.fr/en/facilities/nmr), including 300, 400, 500, 600, 700 and to 800MHz NMR magnets, equipped with solution and solid-state NMR probes.

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MSB Team

NMR Group of Membranes and Protein Assemblies

Methodological Development for Solid-State NMR

SOLID-STATE NMR METHODOLOGY

We develop magic-angle spinning solid-state NMR methods to tackle complex molecular assemblies, such as protein complexes (amyloids, protein filaments), membrane proteins and intact cells and cell walls. Ultra-fast magic-angle spinning NMR techniques are also investigated to improve sensitivity and resolution on complex biomolecular systems.

EPR SPECTROSCOPY

We use both continuous-wave and pulse EPR to study various molecular mechanisms using side-directed spin labelling. In particular, we develop EPR methods to study the structure and dynamics of intrinsically disordered proteins and amyloid assemblies

Strategic Isotopic Labeling

We develop strategic isotope labeling approaches using cell free and heterologous expression systems to achieve selective isotope labeling of biomolecules, such as introducing fluorine probes, specific deuteration or diluting active spins for NMR spectroscopy.

AMYLOID PROTEINS

Amyloids are proteins that can form, under particular conditions, fibrillar aggregates (fibrils, oligomers). We study several amyloid proteins involved in various biological and pathological contexts:

Tau protein

We have a specific interest in the protein tau that is involved in a group of diseases call tauopathies. Tau is an intrinsically disordered protein that can form liquid-liquid phase separation (LLPS) and amyloids. We study the mechanism of amyloid formation and how different aggregation pathways lead to different amyloid structures with different pathological activities. We also investigate tau LLPS and its relationship to amyloid formation. We combine several methods including EPR, cryoEM, NMR and vibrational spectroscopy to study the different aspects of tau.

TMEM106B

TMEM106B is a transmembrane protein increasingly recognized for its complex roles in lysosomal function and its involvement in neurodegenerative processes. It is notably the first amyloid identified to be associated with normal human aging, forming intracellular aggregates that are considered a hallmark of neuronal aging. TMEM106B has been observed to escape from lysosomes, suggesting a disruption in its normal trafficking or degradation, which may contribute to its pathological accumulation. To address these complex and fascinating questions, a combination of solid-state NMR, solution NMR, and cryo-electron microscopy is employed to investigate its structural properties, amyloid conformations, and functional interactions.

Functional amyloids

Amyloids are commonly associated with neurodegenerative diseases and have, more recently, also been identified in programmed cell-death, biofilm formation and other functional mechanisms. We aim at understanding the atomic structural architecture of functional amyloids and study the structure-function relationship and their interactions with molecular partners.

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Membrane proteins and lipid interactions

Membranes, membrane lipids and membrane proteins are main building blocks in cells, regulating essential cellular processes as well as the communication with the extracellular environment. NMR is a primary technique to access structures, dynamics and the physico-chemical properties of lipid and membrane protein assemblies. We use solid-state and solution NMR to study structural and dynamic aspects of the membranes, membrane proteins and membrane lipids and their interactions, for instance in the context of cell division or the formation of myelin membranes

Cell wall, intact cells, and biopolymers

Most bacterial, plant and fungal cells possess at their surface a protective layer called the cell wall, conferring strength, plasticity and rigidity to withstand the osmotic pressure. We develop biophysical methods to study the molecular organization of native cell wall, biofilms and intact cells in yeast, fungi and bacteria, especially to investigate polysaccharides and lipids of the cell surface. The organization of wood biopolymers in grapevine are also deciphered