NMR Perspectives of the KcsA Potassium Channel in the Membrane Environment

Membrane-embedded proteins (MPs) are central to a wide range of cellular processes. Despite their importance, structural studies of MPs are hindered by expression difficulties and the need for stabilization in a membrane-mimicking environment. High-resolution NMR methods can investigate structure and function of MPs due to methodological advances and new membrane-like assemblies for stabilization of MPs. In this perspective of the field, we introduce the challenges and opportunities of NMR studies of membrane proteins, briefly surveying membrane-mimicking systems and their application in structure determination. A case study then focuses on the C-terminal domain of the bacterial potassium channel KcsA, describing how improvements in membrane-mimicking conditions eventually enabled us to present a structural view of the pH-dependent behavior of this cytoplasmic channel domain. The results highlight prerequisites for a successful study of MPs and the potential for future investigations.