Atomic structure of a Na+- and K+-conducting channel

Shi, Ning; Ye, Sheng; Alam, Amer; Chen, Liping; Jiang, Youxing

doi:10.1038/nature04508

Cited by 225 publications

(271 citation statements)

References 27 publications

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“…Our solution NMR provides initial experimental insight into the motion of the NaK channel. FLNaK, which crystallized in the closed form, displays clear peak doubling throughout the spectra (19). This is indicative of two states that interconvert slowly (millisecond-second timescale) (Fig.…”

Section: Discussionmentioning

confidence: 92%

“…This study provides experimental evidence of structural and dynamic coupling between the inner gate and selectivity filter in the NaK channel, a nonselective cation channel from Bacillus cereus (19). These results were entirely unexpected given the available high-resolution crystal structures (20,21).…”

mentioning

confidence: 77%

“…FLNaK provides a good model of the closed state based on both the crystal structure and ion flux assays (Fig. 1C) (19). Initial assessment of this spectrum reveals peak doubling, which reveals that FLNaK exists in two states in isotropic bicelles at 45°C (Fig.…”

Section: Significancementioning

confidence: 95%

“…The NaK channel has the same basic pore architecture as K + channels ( Fig. 1 B and C) and has become a second model system for investigating ion selectivity and gating due to its distinct selectivity filter sequence ( 63 TVGDGN 68 ) and structure (19)(20)(21)(22)(23). Most strikingly, there are only two ion binding sites in the selectivity filter of the nonselective NaK channel (Fig.…”

mentioning

confidence: 99%

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Role of protein dynamics in ion selectivity and allosteric coupling in the NaK channel

Brettmann

Urusova

Tonelli

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Flux-dependent inactivation that arises from functional coupling between the inner gate and the selectivity filter is widespread in ion channels. The structural basis of this coupling has only been well characterized in KcsA. Here we present NMR data demonstrating structural and dynamic coupling between the selectivity filter and intracellular constriction point in the bacterial nonselective cation channel, NaK. This transmembrane allosteric communication must be structurally different from KcsA because the NaK selectivity filter does not collapse under low-cation conditions. Comparison of NMR spectra of the nonselective NaK and potassiumselective NaK2K indicates that the number of ion binding sites in the selectivity filter shifts the equilibrium distribution of structural states throughout the channel. This finding was unexpected given the nearly identical crystal structure of NaK and NaK2K outside the immediate vicinity of the selectivity filter. Our results highlight the tight structural and dynamic coupling between the selectivity filter and the channel scaffold, which has significant implications for channel function. NaK offers a distinct model to study the physiologically essential connection between ion conduction and channel gating.solution NMR | ion channels | membrane protein | protein dynamics

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Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 77%

Section: Significancementioning

confidence: 95%

mentioning

confidence: 99%

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Role of protein dynamics in ion selectivity and allosteric coupling in the NaK channel

Brettmann

Urusova

Tonelli

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Intuitively, this poses a conundrum given our understanding of what constitutes a K + selective ion conduction pore: How can charged ions move across this narrow tunnel whose size is equivalent to a closed tetrameric cation channel gate 19,20,21 ? However, ion permeation through a narrow hydrophobic pathway is not unprecedented.…”

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confidence: 99%

The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture

Lee

Guo

Zeng

et al. 2017

Nature

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TMEM175 is a lysosomal K+ channel important for maintaining the lysosomal membrane potential and pH stability1. It contains two homologous copies of a six-transmembrane (6-TM) domain, which has no sequence homology to the canonical tetrameric K+ channels and lacks the TVGYG selectivity filter motif2–4. Present in a subset of bacteria and archaea, the prokaryotic TMEM175 contains only a single 6-TM domain and functions as a tetramer. Here, we present the crystal structure of a prokaryotic TMEM175 from Chamaesiphon minutus, CmTMEM175, whose architecture represents a completely different fold from that of canonical K+ channels. All six transmembrane helices of CmTMEM175 are tightly packed within each subunit without undergoing domain swap. The highly conserved TM1 acts as the pore lining inner helix, creating an hour-glass shaped ion permeation pathway in the channel tetramer. Three layers of hydrophobic residues on the C-terminal half of TM1s form a bottle neck along the ion conduction pathway and serve as the selectivity filter of the channel. Mutagenesis analysis suggests that the first layer of the highly conserved isoleucine residues in the filter plays the central role in channel selectivity. Thus, the structure of CmTMEM175 represents a novel architecture of a tetrameric cation channel whose ion selectivity mechanism appears distinct from that of the classical K+ channel family.

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Cyclic Nucleotide‐gated Ion Channels

Zheng

Matulef

2009

Encyclopedia of Life Sciences

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Cyclic nucleotide‐gated (CNG) ion channels are activated by cAMP or cGMP, crucial intracellular messenger molecules that regulate a wide variety of physiological activities. In photoreceptors and olfactory neurons, CNG channels play an essential role in transducing sensory stimuli into electrical and chemical responses. CNG channels are also found in other tissues including brain and sperm, where they may contribute to physiological functions including pacemaking, synaptic transmission and chemosensation. The exquisite regulation of different CNG channels by divalent cations, calmodulin, phosphorylation and phospholipids allows these proteins to carry out disparate physiological functions with high precision. Our understanding of the structure of these channels has been greatly enhanced by the recent determination of the structures of domains of related ion channels. The powerful combination of electrophysiology, biochemistry, patch‐clamp fluorometry and X‐ray crystallography has begun to unravel the mystery of how CNG channels are regulated and how the binding of cyclic nucleotides lead to channel opening. Key concepts Ion channels are membrane proteins that allow ions to diffuse across cellular membranes in a regulated manner. CNG channels are ion channels regulated by the direct binding of cyclic nucleotides. Photoreceptors are retinal cells that contain a high density of ion channels regulated by the binding of cyclic nucleotides. Olfaction is the process of odour sensation, also regulated by the binding of cyclic nucleotides. Permeation describes the ability of ion channels to selectively determine which ions can move through them. Gating is the process by which ion channels open and close to control the flow of ions. Structure/function describes the relationship between the 3D structure of an ion channel and its function. Cyclic nucleotides are small ligands used to control the gating of CNG channels.

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Atomic structure of a Na+- and K+-conducting channel

Cited by 225 publications

References 27 publications

Role of protein dynamics in ion selectivity and allosteric coupling in the NaK channel

Role of protein dynamics in ion selectivity and allosteric coupling in the NaK channel

The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture

Cyclic Nucleotide‐gated Ion Channels

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