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Capturing the dynamics of G-protein-coupled receptors (GPCRs) as they transduce extracellular signals into key physiological processes remains one of the most challenging research areas over the last two decades. Meanwhile, more recent attention has turned to the action of solute carriers (SLCs) that comprise both facilitative transporters and secondary active transporters. Because GPCRs and SLCs play critical roles in health and disease, and thereby serve as major targets for drug discovery, much effort has focused on capturing their various conformational states using conventional structural biology techniques. Here, we consider roles that mass spectrometry-based approaches play, particularly with respect to uncovering the impact of phosphorylation, defining ligands, and revealing the action of lipids in modulating interactions, transport, and conformational dynamics.

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