Copper ions are essential for life but posses a redox-activity which makes them potentially toxic, and their cellular availability is highly regulated by an intricate network of intracellular chaperones, transcription factors and membrane transporters. Copper homeostatic imbalance is connected to several major neurological diseases. The detailed mechanisms of copper movement across membranes remain unknown due to the difficulty to characterize at atomic level the different proteins involved, which are mainly integral membrane systems. In humans, high-affinity copper uptake is modulated by hCTR1, a trimeric membrane transporter which has so far fled from high-resolution x-ray or cryo-EM investigations and is extremely challenging to produce and recover in workable amounts for structural studies. The central objective of the present project is to develop and apply a solid-state Magic-Angle Spinning (MAS) NMR approach to allow complete characterization of the structure and mechanism of lipid-bound hCTR1. Building on a decade of continuous advances of the NMR community, the recent development of very fast (up to 100 kHz) MAS probes has revolutionised this field, with developments that speed up the analysis of proteins of considerable size and open the way to complex biological solids available in limited amounts. We propose to leverage the unique expertise and equipment available in the consortium, and achieve the objectives above through a combination of innovative strategies for isotopic sample preparation, advanced spectroscopic tools to obtain NMR signatures of the structure and dynamics, and new instrumentation capable of even faster MAS rates. The project will provide breakthrough data for understanding structure-activity relationships in a challenging integral membrane protein, and will allow the addition of solid-state NMR to the method portfolio for the characterization of medically relevant targets.