Insights into Cholesterol/Membrane Protein Interactions Using Paramagnetic Solid-State NMR.

Cholesterol is an essential component of animal cell membranes and impacts the structure and function of membrane proteins. But how cholesterol exerts its functions remains often enigmatic. Here, high-resolution solid-state NMR in combination with paramagnetic cholesterol analogues was shown to be a powerful approach to study the interaction of membrane proteins with cholesterol. Application of the method to the 169-residue translocator protein TSPO provides residue-specific information about its interaction with cholesterol. Comparison with NMR signal perturbations induced by diamagnetic cholesterol furthermore supports changes in the structure of mammalian TSPO caused by cholesterol binding.