Extended Data Fig. 10: Schematic summary of NHA2 lipid-remodeling and electroneutral exchange.

a. In the presence of PI lipids NHA2 undergoes a conformational change, closing the intracellular gap between protomers to form a more compacted homodimer, which is likely the more active state of the protein; core transport domain (pink), dimer domain (green), additional dimer domain-swapped helix (TM –1 in blue), PI lipid (red) and ion-binding aspartate (red stick). b. NHA2 co-localises with an V-type H⁺-ATPase and the proton (blue-sphere) gradient is used to drive the efflux of sodium (yellow-sphere) from the cytoplasm, with a 1H⁺: 1Na⁺ stoichiometry (and a Na⁺ binding affinity K_D = ~30 mM) into either organelles, for example, lysosomes or across the plasma membrane of specialized cells (components colored as in a).