Voltage-gated ion channels are large tetrameric multidomain membrane proteins that play crucial roles in various cellular transduction pathways. Because of their large size and domain-related mobility, structural characterization has proved challenging. We analyzed high-resolution solid-state NMR data on different isotope-labeled protein constructs of a bacterial cyclic nucleotide-activated K(+) channel (MlCNG) in lipid bilayers. We could identify the different subdomains of the 4×355 residue protein, such as the voltage-sensing domain and the cyclic nucleotide binding domain. Comparison to ssNMR data obtained on isotope-labeled cell membranes suggests a tight association of negatively charged lipids to the channel. We detected spectroscopic polymorphism that extends beyond the ligand binding site, and the corresponding protein segments have been associated with mutant channel types in eukaryotic systems. These findings illustrate the potential of ssNMR for structural investigations on large membrane-embedded proteins, even in the presence of local disorder.