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

Xiaomin Ou,Zhenfeng Liu,Jianli Guo,Longfei Wang,Xiuying Liu,Jianyuan Sun,Hanting Yang

doi:10.1186/s12915-017-0372-8

Abstract

BackgroundTrimeric intracellular cation (TRIC) channels are crucial for Ca2+ 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.ResultsHere 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 Ca2+, Mg2+, 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.ConclusionsThe 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.

Highlights

Trimeric intracellular cation (TRIC) channels are crucial for Ca2+ handling in eukaryotes and are involved in K+ uptake in prokaryotes
Ion- and water-binding sites within an hourglass-shaped pore As shown in Fig. 1, the Sulfolobus solfataricus (SsTRIC) protein reconstituted on giant unilamellar vesicles (GUVs) forms an ion channel permeable to K+ ion and exhibits three major open states with conductances at 42.2 pS, 100.6 pS, and 163.7 pS, respectively
SsTRIC is essentially impermeable to Ca2+, Mg2+, or Cl, as the reversal potential remains close to 0 mV when 75 mM CaCl2 or MgCl2 is added to the bath solution

Summary

Introduction

Trimeric intracellular cation (TRIC) channels are crucial for Ca2+ handling in eukaryotes and are involved in K+ uptake in prokaryotes. The regulated processes of Ca2+ release from the intracellular stores and its uptake from the cytosol are vital for various biological processes including muscle contraction, neurotransmitter release, cell division, and apoptosis [1, 2]. Muscle contraction is initiated by membrane depolarization followed by opening of a ryanodine receptor (RyR) channel to release Ca2+ from the lumen of the sarcoplasmic reticulum (SR) into the cytosol. Efficient operation of E-C coupling requires the RyR to release Ca2+, and counteracting ion channels to restore the balance of the SR membrane potential and maintain ion homeostasis within the SR lumen [4]. Two isoforms of SR/endoplasmic reticulum (ER) membrane proteins, called trimeric intracellular cation (TRIC)

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