Structural basis for ion selectivity in TMEM175 K+ channels

Brunner, Janine D. and Jakob, Roman P. and Schulze, Tobias and Neldner, Yvonne and Moroni, Anna and Thiel, Gerhard and Maier, Timm and Schenck, Stephan. (2020) Structural basis for ion selectivity in TMEM175 K+ channels. eLife, 9. p. 53683.

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Official URL: https://edoc.unibas.ch/76260/

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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 Zn; 2+; . 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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Maier)
UniBasel Contributors:Maier, Timm
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:eLife Sciences Publications
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 Nov 2021 16:05
Deposited On:24 Nov 2021 16:05

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