2.A.19.5.3
Na⁺:Ca²⁺ exchanger, NCX_Mj (3-d structure known at 1.9 Å resolution; PDB# 3V5U (Liao et al., 2012). Contains 10 TMSs with two 5 TMS repeats. Four ion binding sites near the center of the protein are present, one specific for Ca²⁺ and three probably for Na⁺. Two passageways allow for Na⁺ and Ca²⁺ access from the external side.  However see a more recent analysis reported for 2.A.19.8.2 (Nishizawa et al. 2013).  Transport of both Na⁺ and Ca²⁺ requires protonation of D240, but this side chain does not coordinate either ion, implying that the ion exchange stoichiometry is 3:1 and that translocation of Na⁺ across the membrane is electrogenic although transport of Ca²⁺ is not (Marinelli et al. 2014). This system has been reviewed and considered to be a model protein for the entire family (Khananshvili 2021).