Brunner, Janine D. ; Jakob, Roman P. ; Schulze, Tobias ; Neldner, Yvonne ; Moroni, Anna ; Thiel, Gerhard ; Maier, Timm ; Schenck, Stephan (2020)
Structural basis for ion selectivity in TMEM175 K+ channels.
In: eLife, 9
doi: 10.7554/eLife.53683
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
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. 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.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2020 |
| Autor(en): | Brunner, Janine D. ; Jakob, Roman P. ; Schulze, Tobias ; Neldner, Yvonne ; Moroni, Anna ; Thiel, Gerhard ; Maier, Timm ; Schenck, Stephan |
| Art des Eintrags: | Bibliographie |
| Titel: | Structural basis for ion selectivity in TMEM175 K+ channels. |
| Sprache: | Englisch |
| Publikationsjahr: | 8 April 2020 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | eLife |
| Jahrgang/Volume einer Zeitschrift: | 9 |
| DOI: | 10.7554/eLife.53683 |
| Kurzbeschreibung (Abstract): | 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. 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. |
| ID-Nummer: | pmid:32267231 |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Plant Membrane Biophyscis (am 20.12.23 umbenannt in Biologie der Algen und Protozoen) |
| Hinterlegungsdatum: | 14 Apr 2020 06:23 |
| Letzte Änderung: | 14 Apr 2020 06:23 |
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