Structural mechanisms of gating and selectivity of human rod CNGA1 channel

Xue, Jing; Han, Yanping; Zeng, Weizhong; Wang, Yan; Jiang, Youxing

doi:10.1016/j.neuron.2021.02.007

Cited by 48 publications

(77 citation statements)

References 84 publications

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“…CNBDs in mixtures of conformations could also underlie observed subconductances in channels covalently locked into distinct ligand-bound states 55 . We hypothesize that this conformational change involves capping of the CNBD by the C helix along with movement towards the membrane of the CNBD and C-linker connecting the CNBD to the pore lining S6 helix as observed in structural and functional studies [34][35][36][39][40][41] .…”

Section: Discussionmentioning

confidence: 92%

“…Cryo-EM structures of TAX-4 have recently been resolved in both unliganded and fully cGMP-bound states [34][35][36] . These structural snapshots are largely consistent with the above mechanism involving movement of the C helix towards the occupied binding pocket.…”

Section: Discussionmentioning

confidence: 99%

“…Cryo-EM structural models of TAX-4 34,35 , human rod CNGA1 channels 36 , and prokaryotic homologs 37,38 in both unliganded and cGMP/cAMP-bound conformations provide important static snapshots of endpoints during ligand activation. These structures as well as others from prokaryotic homologs 37,38 are complimented by functional studies of channel currents and measures of ligand-dependent conformational changes using approaches such as fluorescence spectroscopy 39 , electron paramagnetic resonance 40 , and high-speed atomic force microscopy 41 .…”

Section: Introductionmentioning

confidence: 99%

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Single-molecule imaging with cell-derived nanovesicles reveals early binding dynamics at a cyclic nucleotide-gated ion channel

Patel

Salinas

et al. 2021

Preprint

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Ligand binding to membrane proteins is critical for many biological signaling processes. However, individual binding events are rarely directly observed, and their asynchronous dynamics are occluded in ensemble-averaged measures. For membrane proteins, single-molecule approaches that resolve these dynamics are challenged by dysfunction in nonnative lipid environments, lack of access to intracellular sites, and costly sample preparation. Here, we introduce an approach combining cell-derived nanovesicles, microfluidics, and single-molecule fluorescence colocalization microscopy to track individual binding events at a cyclic nucleotide-gated TAX-4 ion channel critical for sensory transduction. Our observations reveal dynamics of both nucleotide binding and a subsequent conformational change likely preceding pore opening. We further show that binding of the second ligand in the tetrameric channel is less cooperative than previously estimated from ensemble-averaged binding measures. This approach is broadly applicable to studies of binding dynamics for proteins with extracellular or intracellular domains in native cell membrane.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Single-molecule imaging with cell-derived nanovesicles reveals early binding dynamics at a cyclic nucleotide-gated ion channel

Patel

Salinas

et al. 2021

Preprint

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“…The overall architecture of the AKT1 channel is similar to other non domainswapped ion channels such as the hyperpolarization-activated HCN1 12,13 , KAT1 14 and LliK 15 channels, the depolarization-activated ether-a-go-go channel 16 , and ligand-gated CNGA1 channel 17 . In these channels, the S4 helix from the voltage sensing domain (VSD) that bears the gating charges is linked to the S5 helix of the pore domain via a short loop (1a) such that the pore and voltage sensing domains of the same subunit coalesce together as a bundle.…”

mentioning

confidence: 95%

“…Neighboring AKT1 subunits adopt alternating C-linker conformations: one conformation is termed 'flat', similar in conformation to that seen in LliK 15 and HCN1 12 , while the second conformation is termed 'kinked' and resembles that of KAT1 14 . Variations in Clinker and CNBD / CNBHD architecture have been observed between different channels though the exact nature of these differences is not always clear 7,12,14,15,17,21 . Our structures suggest that these channels may sample multiple conformations during their respective activation cycles, and that there may be direct implications for regulation of electrical activation (2a,b,c,d).…”

mentioning

confidence: 99%

Symmetry reduction in a hyperpolarization-activated homotetrameric ion channel

Dickinson

Gupta

Pourmal

et al. 2021

Preprint

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Plants obtain nutrients from the soil via transmembrane transporters and channels in their root hairs, from which ions radially transport in towards the xylem for distribution across the plant body. We determined structures of the hyperpolarization-activated channel AKT1 from Arabidopsis thaliana, which mediates K+ uptake from the soil into plant roots. These structures of AtAKT1 embedded in lipid nanodiscs show that the channel undergoes a reduction of C4 to C2 symmetry, possibly to regulate its electrical activation.

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Ligand‐Binding Mediated Gradual Ionic Transport in Nanopores

Varol

Förster

Andrieu‐Brunsen

2023

Adv Materials Inter

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Selective binding of metal ions to their receptors at the cell membranes is essential for immune reactions, signaling, and opening/closing of the ion channels. Such ligand‐binding‐based pore activities inspire scientists to build metal‐ion‐responsive mesoporous films that can interact with metal ions to tune the ionic nanopore transport. However, to apply these mesoporous films in novel sensing and separation applications, their ligand‐binding‐triggered ionic pore transport needs to be understood fundamentally toward programming the transport of both anions and cations simultaneously and gradually. Herein, it is shown how Ca2+ ion concentration and attachment to the different chemistry silica nanopores tunes finely the nanopore transport of both anions and cations, especially for phosphate‐containing polyelectrolyte (PMEP) functionalized mesopores. This biased ligand binding can gradually regulate the transport of anions and cations, whereas pores without polymers can gradually regulate only the anionic transport. Last, pore polymer functionality related to Ca2+ ion binding also diverts the pores’ adsorption/desorption (reversibility) response. Almost fully reversible Ca2+ binding is observed in non‐functional pores and non‐reversible Ca2+ binding at the PMEP‐modified pores. It is also demonstrated that non/functional pores, even at sub‐µm concentrations, bind only divalent Ca2+ ions, but they are not selective to trivalent Al3+ ions.

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Structural mechanisms of gating and selectivity of human rod CNGA1 channel

Cited by 48 publications

References 84 publications

Single-molecule imaging with cell-derived nanovesicles reveals early binding dynamics at a cyclic nucleotide-gated ion channel

Single-molecule imaging with cell-derived nanovesicles reveals early binding dynamics at a cyclic nucleotide-gated ion channel

Symmetry reduction in a hyperpolarization-activated homotetrameric ion channel

Ligand‐Binding Mediated Gradual Ionic Transport in Nanopores

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