Structural basis for ion selectivity in TMEM175 K+ channels

Janine D. Brunner, Roman P. Jakob, Tobias Schulze, Yvonne Neldner, Anna Moroni, Gerhard Thiel, Timm Maier, Stephan Schenck

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)
126 Downloads (Pure)


The TMEM175 family constitutes recently discovered K+channels that are important for autophagosome turnover and lysosomal pH regulation and are associated with the early onset of Parkinson Disease. TMEM175 channels lack a P-loop selectivity filter, a hallmark of all known K+ channels, raising the question how selectivity is achieved. Here, we report the X-ray structure of a closed bacterial TMEM175 channel in complex with a nanobody fusion-protein disclosing bound K+ ions. Our analysis revealed that a highly conserved layer of threonine residues in the pore conveys a basal K+ selectivity. An additional layer comprising two serines in human TMEM175 increases selectivity further and renders this channel sensitive to 4-aminopyridine and Zn2+. Our findings suggest that large hydrophobic side chains occlude the pore, forming a physical gate, and that channel opening by iris-like motions simultaneously relocates the gate and exposes the otherwise concealed selectivity filter to the pore lumen.

Original languageEnglish
Article numbere53683
Issue number9
Publication statusPublished - 8 Apr 2020


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