Ion channels articles within Nature Communications

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  • Article
    | Open Access

    Potassium ion channels control K+ permeation across cell membranes and mutations that cause cardiovascular and neural diseases are known. Here, the authors perform NMR measurements with the prototypical K+ channel from Streptomyces lividans, KcsA and characterise the effects of disease causing mutations on the conformational dynamics of K+ channels in a physiological solution environment.

    • Yuta Iwahashi
    • , Yuki Toyama
    •  & Ichio Shimada

  • Article
    | Open Access

    The TRPV1 ion channel is a heat-sensing receptor that is also activated by vanilloid compounds, but the molecular underpinnings of thermosensing have remained elusive. Here authors use in solution NMR on the isolated human TRPV1 S1-S4 domain and show that this domain undergoes a non-denaturing temperature-dependent transition with a high thermosensitivity.

    • Minjoo Kim
    • , Nicholas J. Sisco
    •  & Wade D. Van Horn

  • Article
    | Open Access

    Menthol in mints elicits a coolness sensation by selective activation of TRPM8 ion channel. Here authors dock menthol to TRPM8 and systematically validate their menthol binding models with thermodynamic mutant cycle analysis in functional tests, and shed light on TRPM8 activation by menthol at the atomic level.

    • Lizhen Xu
    • , Yalan Han
    •  & Fan Yang

  • Article
    | Open Access

    Glycinergic synapses play a central role in motor control and pain processing in the central nervous system. Here, authors present cryo-EM structures of the full-length glycine receptors (GlyRs) reconstituted into lipid nanodiscs in the unliganded, glycine-bound and allosteric modulator-bound conformations and reveal global conformational changes underlying GlyR channel gating and modulation.

    • Arvind Kumar
    • , Sandip Basak
    •  & Sudha Chakrapani

  • Article
    | Open Access

    Combining cryo-electron tomography with subtomogram averaging (StA) allows the in situ structure determination of proteins and protein complexes. Here, the authors present the hybrid StA (hStA) workflow that combines the advantages of single particle cryo-EM and StA and consists of a tomographic data collection scheme and a data processing workflow and they demonstrate how hStA can improve the resolution using two examples: the ion channel RyR1 and tobacco mosaic virus.

    • Ricardo M. Sanchez
    • , Yingyi Zhang
    •  & Mikhail Kudryashev

  • Article
    | Open Access

    Small molecule polyamines participate in diverse aspects of cell growth and differentiation and are known to regulate ion channel gating. Here authors reveal that cellular polyamines control nicotinic acetylcholine receptor (nAChR) biogenesis, and either catabolic degradation or inhibition of polyamine production augments nAChR assembly.

    • Madhurima Dhara
    • , Jose A. Matta
    •  & David S. Bredt

  • Article
    | Open Access

    The essential role of ORAI1 channels in receptor-evoked Ca2+ signaling is well understood, but the roles of ORAI2 and ORAI3 remained obscure. Here authors show that ORAI2 and ORAI3 channels multimerize with ORAI1 to expand the range of sensitivity of receptor-activated Ca2+ signals, reflecting their enhanced basal STIM1-binding and heightened Ca2+-dependent inactivation.

    • Ryan E. Yoast
    • , Scott M. Emrich
    •  & Mohamed Trebak

  • Article
    | Open Access

    The role of of voltage-gated sodium channels (Nav) in pacemaking and conduction of the human sinoatrial node is unclear. Here, the authors investigate existence and function of neuronal and cardiac Nav in human sinoatrial nodes, and demonstrate their alterations in explanted human diseased hearts.

    • Ning Li
    • , Anuradha Kalyanasundaram
    •  & Vadim V. Fedorov

  • Article
    | Open Access

    Type VI secretion systems (T6SSs) are used by bacteria to inject toxic effector proteins into neighbouring cells. Here, Mariano et al. show that an antibacterial effector from Serratia marcescens forms cation-selective pores that lead to inner-membrane depolarisation and increased outer-membrane permeability.

    • Giuseppina Mariano
    • , Katharina Trunk
    •  & Sarah J. Coulthurst

  • Article
    | Open Access

    Besides mechanical forces, the mechanosensitive channel Piezo1 is activated by the small molecule Yoda1 through an unknown mechanism. Here, using molecular dynamics simulations, calcium imaging and electrophysiology, the authors identify an allosteric Yoda1 binding pocket located in the putative mechanosensory domain.

    • Wesley M. Botello-Smith
    • , Wenjuan Jiang
    •  & Yun Luo

  • Article
    | Open Access

    The transient receptor potential channel member 2 (TRPM2) ion channel has a function in redox-dependent signaling. Here the authors present the cryo-EM structures of zebrafish TRPM2 in the ligand-free form, with Ca2+ and both ADP-ribose/Ca2+ and observe two-fold symmetric quaternary structure rearrangements in the ligand-bound structures that likely represent intermediate gating states.

    • Ying Yin
    • , Mengyu Wu
    •  & Seok-Yong Lee

  • Article
    | Open Access

    CASTOR is a Lotus japonicus ion channel required for nuclear Ca2+ spiking and establishing rhizobial and mycorrhizal symbioses. Here, via structural and functional analysis, Kim et al. show that CASTOR is a Ca2+-selective channel activated via Ca2+ binding to a soluble gating ring consisting of tandem RCK domains.

    • Sunghoon Kim
    • , Weizhong Zeng
    •  & Youxing Jiang

  • Article
    | Open Access

    The sinus node generates rhythmic heartbeat but the molecular basis of pacemaking is still under debate. Here, the authors combine quantitative proteomics and single-nucleus transcriptomics to characterize the molecular composition of the sinus node and provide insights into the underpinnings of pacemaking.

    • Nora Linscheid
    • , Sunil Jit R. J. Logantha
    •  & Alicia Lundby

  • Article
    | Open Access

    The leading cause of cystic fibrosis is the deletion of phenylalanine 508 (F508del) in the first nucleotide-binding domain (NBD1) of the cystic fibrosis transmembrane conductance regulator (CFTR). Here authors we develop nanobodies targeting NBD1 of human CFTR and demonstrate their ability to stabilize both isolated NBD1 and full-length protein.

    • Maud Sigoillot
    • , Marie Overtus
    •  & Cedric Govaerts

  • Article
    | Open Access

    Endoplasmic reticulum Ca2+ sensing STIM proteins and plasma membrane Orai1 channels together regulate Ca2+ influx in eukaryotic cells. Here authors show that two Ca2+-dependent transcription factors, NFAT1 and c-fos, have different requirements for the number of STIM1-Orai1 clusters and on the Ca2+ flux through the clusters.

    • Yu-Ping Lin
    • , Daniel Bakowski
    •  & Anant B. Parekh

  • Article
    | Open Access

    Opening of G protein-gated inwardly rectifying potassium channels (GIRK) is coupled to the activation of a GPCR. Here the authors use NMR and cell-based BRET assays to gain insights into the mechanisms underlying family-specific activation and find that pre-formation of the Gαi/oβγ-GIRK complex in the inactive state is responsible for specific GIRK activation and present a structural model for the Gαi/oβγ-GIRK complex.

    • Hanaho Kano
    • , Yuki Toyama
    •  & Ichio Shimada

  • Article
    | Open Access

    TMEM16F is an enigmatic Ca2 + -activated phospholipid scramblase (CaPLSase) that passively transports phospholipids. Here authors identify an inner activation gate and its disruption profoundly alters TMEM16F phospholipid permeation.

    • Trieu Le
    • , Zhiguang Jia
    •  & Huanghe Yang

  • Article
    | Open Access

    G-protein-gated inward rectifying potassium channels (GIRKs) require Gβγ subunits and phosphorylated phosphatidylinositides (PIPs) for gating. Here authors use native ion mobility mass spectrometry to monitor small molecule binding events to GIRK2 and shed light on the selectivity of GIRK2 towards PIPs.

    • Yang Liu
    • , Catherine E. LoCaste
    •  & Arthur Laganowsky

  • Article
    | Open Access

    Piezo channels are mechanosensitive and rely on membrane composition to transduce physical stimuli into electrical signals. Here authors analyse the membrane components that modulate Piezo1 function using lipid profiling which shows that fatty acid metabolism can modulate ion channel activity.

    • Luis O. Romero
    • , Andrew E. Massey
    •  & Valeria Vásquez

  • Article
    | Open Access

    Two-photon absorption capacity of azobenzene photoswitches usually comes with a reduction in thermal stability. Here, the authors developed photoswitches with high two-photon sensitivity and enhanced cis isomer thermal lifetime for the control of glutamate receptors.

    • Gisela Cabré
    • , Aida Garrido-Charles
    •  & Ramon Alibés

  • Article
    | Open Access

    Allostery is a fundamental principle of protein regulation that remains challenging to engineer. Here authors screen human Inward Rectifier K + Channel Kir2.1 for permissibility to domain insertions and propose that differential permissibility is a metric of latent allosteric capacity in Kir2.1.

    • Willow Coyote-Maestas
    • , Yungui He
    •  & Daniel Schmidt

  • Article
    | Open Access

    Spontaneous activity shifts at constant experimental conditions are widespread among ion channels but the molecular origins are poorly understood. Here, using solid-state NMR and MD simulations, the authors reveal that modal gating shifts in K + channels are caused by large shifts in the channel dynamics which perturb the selectivity filter.

    • Shehrazade Jekhmane
    • , João Medeiros-Silva
    •  & Markus Weingarth

  • Article
    | Open Access

    The helical transmembrane segments of membrane proteins play central roles in sensory transduction but the mechanistic basis for their function remains unresolved. Here the authors identify regions in the S4 voltage-sensing segment of Shaker potassium channels where local helical structure is reliant upon backbone amide support.

    • Daniel T. Infield
    • , Kimberly Matulef
    •  & Francis I. Valiyaveetil

  • Article
    | Open Access

    In plants, hyperosmolality stimuli triggers opening of the osmosensitive channels, leading to a rapid downstream signaling cascade. Here, the authors solve the cryo-EM structure of an osmosensitive channel from Arabidopsis OSCA1.2 in its inactivated state.

    • Xin Liu
    • , Jiawei Wang
    •  & Linfeng Sun

  • Article
    | Open Access

    Transient receptor potential vanilloid channel 3 (TRPV3) responds to temperature and sensitizes upon repeated stimulation with either heat or agonists. Here authors present the cryo-EM structures of apo and sensitized human TRPV3 and describe the structural basis of sensitization.

    • Lejla Zubcevic
    • , Mark A. Herzik Jr.
    •  & Seok-Yong Lee

  • Article
    | Open Access

    Giant cell lesions of the jaw (GCLJ) are debilitating benign tumors of unclear origin. The authors identify driver recurrent somatic mutations in TRPV4, KRAS and FGFR1 and show they converge on aberrant activation of the MAPK pathway. Their findings extend the spectrum of TRPV4 channelopathies and provide rationale for targeted therapies at the bedside in GCLJ.

    • Carolina Cavalieri Gomes
    • , Tenzin Gayden
    •  & Nada Jabado

  • Article
    | Open Access

    The number of K+ occupied binding sites in the selectivity filter of potassium ion channels is still under debate. Here, the authors collect diffraction data on the K+ selective NaK channel NaK2K at a wavelength of 3.35 Å, close to the K absorption edge, revealing that all four binding sites in the selectivity filter are fully occupied by K+ ions.

    • Patricia S. Langan
    • , Venu Gopal Vandavasi
    •  & Leighton Coates

  • Article
    | Open Access

    Transient receptor potential mucolipin 1 (TRPML1) is a lysosomal channel which maintains the low pH and calcium levels for lysosomal function. Here authors use structural biology and electrophysiology to show how lipids bind and allosterically activate TRPML1.

    • Michael Fine
    • , Philip Schmiege
    •  & Xiaochun Li

  • Article
    | Open Access

    Acute bronchoconstriction is the leading cause of asthmatic sudden death following allergen exposure. The authors show that the systemic increase of LPA following inhaled allergen or bradykinin challenge activates the carotid bodies through TRPV1 and LPA-specific receptors and that systemic TRPV1 and LPA-specific receptor antagonists ameliorate acute bronchoconstriction.

    • Nicholas G. Jendzjowsky
    • , Arijit Roy
    •  & Richard J. A. Wilson

  • Article
    | Open Access

    Human Bestrophin1 (hBest1), a calcium-activated chloride channel in retinal pigment epithelium (RPE), is essential for retina physiology. Using electrophysiological and structural approaches, the authors uncover an ATP-dependent activation mechanism of hBest1, and identify an ATP-binding motif.

    • Yu Zhang
    • , Alec Kittredge
    •  & Tingting Yang

  • Article
    | Open Access

    The capsaicin receptor TRPV1 has been structurally characterized, but the capsaicin activation dynamics remain elusive. Here authors use fluorescent unnatural amino acid incorporation, computational modeling and Φ-analysis to derive the capsaicin-bound open state model and reveal the capsaicin induced conformational changes.

    • Fan Yang
    • , Xian Xiao
    •  & Jie Zheng

  • Article
    | Open Access

    Manipulation of the pancreas during surgery can induce acute pancreatitis due to zymogen activation. Here the authors show that the mechanoreceptor Piezo1 is activated by pressure and its activation leads to calcium dependent pancreatic injury whereas its inhibition is protective against pancreatitis.

    • Joelle M.-J. Romac
    • , Rafiq A. Shahid
    •  & Rodger A. Liddle

  • Article
    | Open Access

    Polycystic kidney disease 2-like 1 protein (PKD2L1) is a voltage-dependent calcium-dependent nonselective ion channel involved in sour taste perception and regulation of pH-dependent action potential of spinal cord neurons. Here the authors present the 3.4 Å cryo-EM structure of PKD2L1 in the open state and propose a model for the gating mechanism.

    • Qiang Su
    • , Feizhuo Hu
    •  & Tingliang Wang

  • Article
    | Open Access

    The authors have previously shown that membrane voltage can influence embryonic patterning during development. Here, the authors computationally model how nicotine disrupts Xenopus embryogenesis by perturbing voltage gradients, and rescue nicotine-inducted defects with HCN2 channel expression.

    • Vaibhav P. Pai
    • , Alexis Pietak
    •  & Michael Levin

  • Article
    | Open Access

    Despite being highly toxic, carbon monoxide (CO) is also essential as an intracellular signalling molecule, but CO-dependent signalling is poorly understood. Here, authors employ spectroscopic and electrophysiology methods and find that CO activates KATP channels via SUR2A, a heme-regulated receptor.

    • Sofia M. Kapetanaki
    • , Mark J. Burton
    •  & Emma Raven

  • Article
    | Open Access

    Capsaicin prevents atherosclerotic plaque formation by activating TRPV1 cation channels, but its toxicity precludes its use in clinical settings. Here, Tang and colleagues use copper sulfide nanoparticles as a photothermal switch to locally and temporally activate TRPV1 in vascular smooth muscle cells and reduce plaque formation without apparent toxicity.

    • Wen Gao
    • , Yuhui Sun
    •  & Bo Tang

  • Article
    | Open Access

    IP3 receptors mediate Ca2+ release from the endoplasmic reticulum. Here the authors show that only a small fraction of IP3 receptors initiate Ca2+ signals; these immobile IP3 receptors adjacent to the plasma membrane are optimally placed to control STIM1-dependent Ca2+ entry.

    • Nagendra Babu Thillaiappan
    • , Alap P. Chavda
    •  & Colin W. Taylor

  • Article
    | Open Access

    P2X receptors are nonselective cation channels that are gated by extracellular ATP. Here the authors present the crystal structure of chicken P2X7 with its bound competitive antagonist TNP-ATP and give mechanistic insights into TNP-ATP dependent inhibition through further computational analysis and electrophysiology measurements.

    • Go Kasuya
    • , Toshiaki Yamaura
    •  & Osamu Nureki

  • Article
    | Open Access

    TREKs are members of the two-pore domain potassium (K2P) channels, being important clinical targets. Here the authors identify inhibitors of K2P that bind to an allosteric site located in their extracellular cap, suggesting that it might be a promising drug target for these channels.

    • Qichao Luo
    • , Liping Chen
    •  & Huaiyu Yang

  • Article
    | Open Access

    MgtE is an Mg2+ transporter involved in Mg2+ homeostasis. Here, the authors report that ATP regulates the Mg+2-dependent gating of MgtE and use X-ray crystallography combined with functional studies to propose the molecular mechanisms involved in this process.

    • Atsuhiro Tomita
    • , Mingfeng Zhang
    •  & Osamu Nureki

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