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

Structural basis for ion selectivity in TMEM175 K+ channels

  • Brunner, Janine D ORCID Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium
  • Jakob, Roman P Department Biozentrum, University of Basel, Basel, Switzerland
  • Schulze, Tobias Membrane Biophysics, Technical University of Darmstadt, Darmstadt, Germany
  • Neldner, Yvonne Department of Biochemistry, University of Zürich, Zürich, Switzerland
  • Moroni, Anna ORCID Department of Biosciences, University of Milano, Milan, Italy
  • Thiel, Gerhard Membrane Biophysics, Technical University of Darmstadt, Darmstadt, Germany
  • Maier, Timm ORCID Department Biozentrum, University of Basel, Basel, Switzerland
  • Schenck, Stephan Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium
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  • 2020-4-8
Published in:
  • eLife. - eLife Sciences Publications, Ltd. - 2020, vol. 9
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology
General Neuroscience
General Medicine
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://folia.unifr.ch/global/documents/110499
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