The superfamily of P-loop channels includes potassium, sodium, calcium, cyclic-nucleotide gated, two-pore, and transit receptor potential channels, as well as ionotropic glutamate receptors. Despite the large functional diversity, all members of the superfamily have conserved folding of transmembrane helices in the tetrameric or pseudo-tetrameric pore-forming module where each monomer has either two (2TM) or six (6-TM) transmembrane segments. We elaborated a universal residue-labeling scheme for