A novel tetrameric potassium channel

Youxing Jiang group (University of Texas Southwestern Medical Center)

 

TMEM175 was recently identified as a lysosomal K+ channel in eukaryotes important for setting the lysosomal membrane potential, maintaining pH stability under starved conditions, and regulating autophagosome/lysosome fusion. TMEM175 bears no sequence similarity to canonical K+ channels and also lacks the highly-conserved TVGYG signature sequence. The group of Youxing Jiang at the University of Texas Southwestern Medical Center determined the crystal structure of a prokaryotic TMEM175 homolog from Chamaesiphon minutus (CmTMEM175). The structure revealed a novel architecture for a tetrameric cation channel whose ion-selectivity mechanism is distinct from that of the classical K+ channels. Each CmTMEM175 subunit contains a six-helix-transmembrane (6-TM) domain and four subunits enclose an hour-glass-shaped ion-permeation pathway in the channel tetramer. Three layers of hydrophobic residues on the C-terminal half of each TM1 form a bottleneck along the ion conduction pathway and serve as the channel selectivity filter. Thus, the structure of CmTMEM175 reveals a hitherto unseen ion-channel mechanism for K+ selectivity.

Figure: A cutaway of the TMEM175 tetramer, with the insert showing three layers of hydrophobic residues that form a bottleneck along the ion channel in yellow.

 

Citation: Lee, C, Guo, J, Zeng, W, Kim, S, She, J, Cang, C, Ren, D, Jiang, Y. The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture, Nature 547, 472-475 (2017). DOI: 10.1038/nature23269

 

 


GM/CA @ APS Sponsors: National Institute of General Medical Sciences (NIGMS) and National Cancer Institute (NCI) of the National Institutes of Health (NIH).

  APS is an Office of Science User Facility operated for the U.S. Department of Energy by Argonne National Laboratory

  UChicago Argonne LLC | Privacy & Security Notice | Contact Us | A-Z Index | Search