Fig. 1

Structural features of SpSLC9C1. a Transmembrane topology of Escherichia coli NhaA (EcNhaA), Methanocaldococcus jannaschii NhaP1 (MjNhaP1), and sea urchin Strongylocentrotus purpuratus SLC9C1 (SpSLC9C1); VSD voltage-sensing domain, CNBD cyclic nucleotide-binding domain. Amino acids that may participate in Na⁺ coordination are highlighted (black dots). Asterisks indicate conserved Arg residues that are relevant for Na⁺/H⁺ antiport; Arg320 and Arg347 in MjNhaP1; Arg399 and Arg431 in SpSLC9C1. An Arg is substituted by Lys300 in EcNhaA. b Scheme of the trigonal bi-pyramidal structure of the Na⁺ coordination site from MjNhaP1. Numbers refer to the respective amino-acid residues in E. coli (blue), M. jannaschii (red), and S. purpuratus (black). c Sequence comparison of the VSD from several SLC9C1 members with the canonical VSD of Drosophila Shaker K⁺ channel (DmShaker) and Ciona intestinalis voltage-sensor-containing-phosphatase (CiVSP). S. purpuratus (SpSLC9C1), H. sapiens (HsSLC9C1), M. musculus (MmSLC9C1), C. intestinalis (CiSLC9C1), and spotted gar L. oculatus (LoSLC9C1). Voltage sensors carry conserved positively charged residues in S4 (blue) and conserved negatively charged amino acids in S1–S3 (red). d Cyclic nucleotide-binding domains from sea urchin (SpSLC9C1), human (HsSLC9C1) and mouse (MmSLC9C1) SLC9C1, mouse HCN channel MmHCN2, bovine CNG channel bCNGA1, and C. elegans CNG channel (CeTAX4). The CNBD comprises three α-helices (αA, αB, and αC), eight β-strands (β1–β8), and a phosphate-binding cassette (PBC). Highlighted key residues are the purine-binding residues Val and Leu (β4 and β5), the ribofuranose-binding residues Gly/Glu (β6), the phosphate-binding residues Arg/Thr, and the purine-binding Arg in αC of MmHCN2