TMEM175 homologue of 197 aas and 5 or 6 TMSs. It is a lysosomal K+ channel that is important for maintaining the membrane potential and pH stability of lysosomes. It contains two homologous copies of a 6 TMS domain, which has no sequence homology to the canonical tetrameric K+ channels and lacks the TVGYG selectivity filter motif found in these channels (Lee et al. 2017). The architecture represents a completely different fold from that of canonical K+ channels. All six transmembrane helices of CmTMEM175 are tightly packed within each subunit without undergoing domain swapping. The highly conserved TMS1 helix acts as the pore-lining inner helix, creating an hourglass-shaped ion permeation pathway in the channel tetramer. Three layers of hydrophobic residues on the carboxy-terminal half of the TMS1 form a bottleneck along the ion conduction pathway and serve as the selectivity filter. Mutagenesis analyses suggested that the first layer of the highly conserved isoleucine residues in the filter is primarily responsible for channel selectivity. Thus, the structure of CmTMEM175 represents a novel architecture of a tetrameric cation channel whose ion selectivity mechanism appears to be distinct from that of the classical K+ channel family (Lee et al. 2017).
|Protein Name:||Putative integral membrane protein|
|Species:||Chamaesiphon minutus PCC 6605  |
|Number of TMSs:||5|
1: MVKGRLEAFS DGVIAIIITI MVLELKVPHG ETFAALTPLI PVFLSYILSF IYIAIYWNNH
61: HHLLQAVRHV NGRILWANVH LLFWLSLIPF VTAWMGENQF APIPAALYGA VLLFCAIAYL
121: ILTITLIAHH GRESELAIAI GRDFKGKVSL AFYVVGILLS FVNSWLACGI YALVAAMWLI
181: PDRRIERTLV SENLSNK