Correlating ion channel structure and function

Schmidpeter, Philipp A. M.; Nimigean, Crina M.

doi:10.1016/bs.mie.2021.02.016

Cited by 5 publications

(3 citation statements)

References 75 publications

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Section: Resultssupporting

confidence: 79%

“…Sealing lipid bilayers could be formed, regardless of lipid composition, but in the absence of cardiolipin, only very small levels of ion channel activation were observed, as reported previously. 53 Upon cAMP addition, membrane resistance decreased by around 3 orders of magnitude in lipid bilayers containing CL. Along with a decrease in membrane resistance, the capacitance of the membrane increased by a factor of 2–4, which can be attributed to an increase in water content of the ion channels and to the population of the submembrane reservoir by ions as reported previously.…”

Section: Resultsmentioning

confidence: 99%

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Native Function of the Bacterial Ion Channel SthK in a Sparsely Tethered Lipid Bilayer Membrane Architecture

et al. 2023

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The plasma membrane protects the interiors of cells from their surroundings and also plays a critical role in communication, sensing, and nutrient import. As a result, the cell membrane and its constituents are among the most important drug targets. Studying the cell membrane and the processes it facilitates is therefore crucial, but it is a highly complex environment that is difficult to access experimentally. Various model membrane systems have been developed to provide an environment in which membrane proteins can be studied in isolation. Among them, tethered bilayer lipid membranes (tBLMs) are a promising model system providing a solvent-free membrane environment which can be prepared by self-assembly, is resistant to mechanical disturbances and has a high electrical resistance. tBLMs are therefore uniquely suitable to study ion channels and charge transport processes. However, ion channels are often large, complex, multimeric structures and their function requires a particular lipid environment. In this paper, we show that SthK, a bacterial cyclic nucleotide gated (CNG) ion channel that is strongly dependent on the surrounding lipid composition, functions normally when embedded into a sparsely tethered lipid bilayer. As SthK has been very well characterized in terms of structure and function, it is well-suited to demonstrate the utility of tethered membrane systems. A model membrane system suitable for studying CNG ion channels would be useful, as this type of ion channel performs a wide range of physiological functions in bacteria, plants, and mammals and is therefore of fundamental scientific interest as well as being highly relevant to medicine.

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Section: Resultssupporting

confidence: 79%

Section: Resultsmentioning

confidence: 99%

Native Function of the Bacterial Ion Channel SthK in a Sparsely Tethered Lipid Bilayer Membrane Architecture

et al. 2023

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“…To test whether BtCap14 displays ion channel activity we reconstituted the detergent-solubilized complex in artificial lipid bilayers and directly measured ion flux across the membrane using voltage-clamp electrophysiology (Fig. S4A) (22)(23)(24). In this assay, the voltage is held constant creating a driving force, and ion flux is measured by the resulting change in current.…”

Section: Cap14 Is a 2′3′-cgamp-activated Ion Channelmentioning

confidence: 99%

Bacterial cGAS-like enzymes produce 2′,3′-cGAMP to activate an ion channel that restricts phage replication

Tak,

Walth,

Whiteley

2023

Preprint

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The mammalian innate immune system uses cyclic GMP–AMP synthase (cGAS) to synthesize the cyclic dinucleotide 2′,3′-cGAMP during antiviral and antitumor immune responses. 2′,3′-cGAMP is a nucleotide second messenger that initiates inflammatory signaling by binding to and activating the stimulator of interferon genes (STING) receptor. Bacteria also encode cGAS/DncV-like nucleotidyltransferases (CD-NTases) that produce nucleotide second messengers to initiate antiviral (antiphage) signaling. Bacterial CD-NTases produce a wide range of cyclic oligonucleotides but have not been documented to produce 2′,3′-cGAMP. Here we discovered bacterial CD-NTases that produce 2′,3′-cGAMP to restrict phage replication. Bacterial 2′,3′-cGAMP binds to CD-NTase associated protein 14 (Cap14), a transmembrane protein of unknown function. Using electrophysiology, we show that Cap14 is a chloride-selective ion channel that is activated by 2′,3′-cGAMP binding. Cap14 adopts a modular architecture, with an N-terminal transmembrane domain and a C-terminal nucleotide-binding SAVED domain. Domain-swapping experiments demonstrated the Cap14 transmembrane region could be substituted with a nuclease, thereby generating a biosensor that is selective for 2′,3′-cGAMP. This study reveals that 2′,3′-cGAMP signaling extends beyond metazoa to bacteria. Further, our findings suggest that transmembrane proteins of unknown function in bacterial immune pathways may broadly function as nucleotide-gated ion channels.

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Anionic lipids unlock the gates of select ion channels in the pacemaker family

Schmidpeter

Rheinberger

et al. 2022

Nat Struct Mol Biol

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Correlating ion channel structure and function

Cited by 5 publications

References 75 publications

Native Function of the Bacterial Ion Channel SthK in a Sparsely Tethered Lipid Bilayer Membrane Architecture

Native Function of the Bacterial Ion Channel SthK in a Sparsely Tethered Lipid Bilayer Membrane Architecture

Bacterial cGAS-like enzymes produce 2′,3′-cGAMP to activate an ion channel that restricts phage replication

Anionic lipids unlock the gates of select ion channels in the pacemaker family

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