Ion channels have been long recognized as one of the largest cell signaling superfamilies, underlying numerous critical health related phenomena. Dynamic allosteric processes in ion channels control key aspects of signaling, including inactivation and mean open time. Solid state NMR experiments on full length wild type channel in proteo-liposomes provide evidence for evacuation of ions from the selectivity filter during inactivation and thermodynamic coupling between channel opening and ion affinity. Furthermore, these experiments have identified residues that serve as “hotspots” for allostery. We examine an intermediate of the opening process and its conformational exchange processes. We also report progress on very high order oligomeric proteins including amyloids involved in cell signaling in human health and disease, and studies using solid-state NMR.