FXYD protein primary and tertiary structures. (A) Amino acid sequence alignment of human FXYD proteins. Signal sequences are orange, the extracellular domain is purple with the FXYD motif highlighted in green, the TM domain is black with two red conserved glycine residues, and the cytoplasmic domain is blue. The sequence numbering starts with the first purple residue in the extracellular domain. (B–D) NMR structures of human PLM (B), human γ subunit (C), and rat CHIF (D) proteins. When available, structures show overlay of all possible configurations obtained from NMR analysis. Conserved residues are highlighted in the structure. The FXYD motif is green and two glycine residues are red. FXYD5’s longer N terminus is shown in the top part of the sequence alignment. Structures are made with the PLM, γ subunit, and CHIF structures (PBD accession nos. 2OJ1, 2MKV, and 2JP3, respectively) with approximate position of the lipid bilayer according to Geering (2006).