Fig. 1: The cryo-EM structure of NHA2 reveals a domain-swapped homodimer.
From: Structure, mechanism and lipid-mediated remodeling of the mammalian Na+/H+ exchanger NHA2
a, Phylogenetic tree of the canonical human NHE1–9 (SLC9A1–9) cluster compared to human NHA1 and NHA2 (SLC9B1–2) and bacterial members NapA (Thermus thermophilus), NhaP1 (Methanococcus janashi), NhaP (Pyrococcus abyssi) and NhaA (Escherichia coli). b, Cryo-EM density map of NHA2ΔN in detergent, showing the 6-TM core ion transport domains (colored in pink), the dimer domain (colored in green) and the N-terminal domain-swapped helix, TM –1 (colored in blue). c, Cartoon representation of dimeric NHA2 from the side (left) and a top view from the extracellular side (right). The ion-translocation 6-TM domain (transport) is colored in pink, the dimerization domain in green and the N-terminal domain-swapped transmembrane helix (TM –1) in blue, with the respective transmembrane helices enumerated. Inset (dashed box): cartoon representation from the extracellular side, with each monomer colored individually. d, Cartoon representation of the 14-TM NHA2 monomer from the extracellular side and colored as in c, superimposed onto the 13-TM outward-facing structure of NapA (PDB 4BWZ) in gray. e, Cartoon representation of the NapA homodimer, colored as for NHA2 in c to highlight that, in the absence of the additional N-terminal helix TM –1, an extensive and more compact oligomer is formed compared to NHA2.
