Ion- and water-binding sites inside an occluded hourglass pore of a trimeric intracellular cation (TRIC) channel

BACKGROUND: Trimeric intracellular cation (TRIC) channels are crucial for Ca(2+) handling in eukaryotes and are involved in K(+) uptake in prokaryotes. Recent studies on the representative members of eukaryotic and prokaryotic TRIC channels demonstrated that they form homotrimeric units with the ion-conducting pores contained within each individual monomer. RESULTS: Here we report detailed insights into the ion- and water-binding sites inside the pore of a TRIC channel from Sulfolobus solfataricus (SsTRIC). Like the mammalian TRIC channels, SsTRIC is permeable to both K(+) and Na(+) with a slight preference for K(+), and is nearly impermeable to Ca(2+), Mg(2+), or Cl(–). In the 2.2-Å resolution K(+)-bound structure of SsTRIC, ion/water densities have been well resolved inside the pore. At the central region, a filter-like structure is shaped by the kinks on the second and fifth transmembrane helices and two nearby phenylalanine residues. Below the filter, the cytoplasmic vestibule is occluded by a plug-like motif attached to an array of pore-lining charged residues. CONCLUSIONS: The asymmetric filter-like structure at the pore center of SsTRIC might serve as the basis for the channel to bind and select monovalent cations. A Velcro-like plug-pore interacting model has been proposed and suggests a unified framework accounting for the gating mechanisms of prokaryotic and eukaryotic TRIC channels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12915-017-0372-8) contains supplementary material, which is available to authorized users.