Back
Structural basis for ion selectivity in TMEM175 K+ channels.
Journal article

Structural basis for ion selectivity in TMEM175 K+ channels.

  • Brunner JD Department of Biochemistry, University of Zürich, Zürich, Switzerland.
  • Jakob RP Department Biozentrum, University of Basel, Basel, Switzerland.
  • Schulze T Membrane Biophysics, Technical University of Darmstadt, Darmstadt, Germany.
  • Neldner Y Department of Biochemistry, University of Zürich, Zürich, Switzerland.
  • Moroni A Department of Biosciences, University of Milano, Milan, Italy.
  • Thiel G Membrane Biophysics, Technical University of Darmstadt, Darmstadt, Germany.
  • Maier T Department Biozentrum, University of Basel, Basel, Switzerland.
  • Schenck S Department of Biochemistry, University of Zürich, Zürich, Switzerland.
Show more…
  • 2020-04-09
Published in:
  • eLife. - 2020
E. coli
human
ion channel
macrobody
molecular biophysics
nanobody
parkinson disease
potassium channel
selectivity filter
structural biology
English 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.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/30297
Statistics
Document views: 35 File downloads: