Structural basis for ion selectivity in TMEM175 K<sup>+</sup> channels

TitleStructural basis for ion selectivity in TMEM175 K+ channels
Publication TypeJournal Article
Year of Publication2018
AuthorsBrunner, J. D., R. P. Jakob, T. Schulze, Y. Neldner, A. Moroni, G. Thiel, T. Maier, and S. Schenck
JournalbioRxiv
Pagination480863
Abstract

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.

URLhttps://www.biorxiv.org/content/biorxiv/early/2018/12/04/480863.full.pdf
DOI10.1101/480863
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