PT  - JOURNAL ARTICLE
AU  - Janine D. Brunner
AU  - Roman P. Jakob
AU  - Tobias Schulze
AU  - Yvonne Neldner
AU  - Anna Moroni
AU  - Gerhard Thiel
AU  - Timm Maier
AU  - Stephan Schenck
TI  - Structural basis for ion selectivity in TMEM175 K<sup>+</sup> channels
AID  - 10.1101/480863
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 480863
4099  - http://biorxiv.org/content/early/2018/12/04/480863.short
4100  - http://biorxiv.org/content/early/2018/12/04/480863.full
AB  - The TMEM175 family constitutes recently discovered K+ channels that lack signatures for a P-loop selectivity filter, a hallmark of all known K+ channels. This raises the question how selectivity in TMEM175 channels is achieved. Here we report the X-ray structure of a bacterial TMEM175 family member in complex with a novel chaperone built of a nanobody fusion-protein. The structure of the channel in a non-conductive conformation was solved at 2.4 Å and revealed bound K+ ions along the channel pore. A hydrated K+ ion at the extracellular pore entrance that could be substituted with Cs+ and Rb+ is coordinated by backbone-oxygens forming a cation-selective filter at the tip of the pore-lining helices. Another K+ ion within the pore indicates the passage of dehydrated ions. Unexpectedly, a highly conserved threonine residue deeper in the pore conveys the K+ selectivity. The position of this threonine in the non-conductive state suggests major conformational rearrangements of the pore-lining helices for channel opening, possibly involving iris-like motions.