Structure of the Na+/H+ exchanger catalytical core. A, the central parts of TM domains IV, V, X, and XI, the presumed catalytical core for hNHE1-catalyzed Na+/H+ exchange, are represented as a ribbon diagram. B, schematic depiction of the central core of NHE1 (left panel) and NhaA (right panel). The amino acid side chains suggested to directly participate in ion translocation are shown. The positions of the main spin labels are shown in red in hNHE1. Note that the characteristic crossover by the extended structures of helices IV and XI results in energetically unfavorable dipole-dipole pairings (dipoles shown as δ+ and δ−) at the ends of the disrupted α-helices.