Transient receptor potential channels articles within Nature Communications

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  • Article
    | Open Access

    Long-chain acyl-Coenzyme-A is a metabolic intermediate with important signaling functions. Here the authors show that it activates the Ca2+ selective ion channels TRPV5 and TRPV6 and elucidate the structural basis of TRPV5 activation using CryoEM.

    • Bo-Hyun Lee
    • , José J. De Jesús Pérez
    •  & Tibor Rohacs

  • Article
    | Open Access

    Neuberger et al. report the structure of human channel TRPV6 in complex with a cannabinoid inhibitor tetrahydrocannabivarin (THCV) and explore the pathway taken by the drug to reach binding sites in the portals that connect the membrane environment to the central cavity of the ion channel pore.

    • Arthur Neuberger
    • , Yury A. Trofimov
    •  & Alexander I. Sobolevsky

  • Article
    | Open Access

    Despite TRPV4’s medical importance, the mechanisms of ligand-mediated channel gating and its regulation by Rho GTPase are unclear. Here, the authors report the structures of TRPV4 in complex with RhoA and ligands, offering atomic-level insights into their functions.

    • Do Hoon Kwon
    • , Feng Zhang
    •  & Seok-Yong Lee

  • Article
    | Open Access

    Nadezhdin et al. present structures of human TRPV4 in complex with the GTPase RhoA, in the apo, agonist 4α-PDD and antagonist HC-067047 bound states, uncovering the mechanisms of channel activation, inhibition and disease-causing mutations.

    • Kirill D. Nadezhdin
    • , Irina A. Talyzina
    •  & Alexander I. Sobolevsky

  • Article
    | Open Access

    A drastic TRPA1 mutant was identified in patients with CRAMPT syndrome, but it has not been functionally characterized. Here, the authors find this mutant confers gain-of-function by co-assembling with wild type protein to form hyperactive channels.

    • Avnika Bali
    • , Samantha P. Schaefer
    •  & Candice E. Paulsen

  • Article
    | Open Access

    Authors present the structural mechanisms of TRPM7 spontaneous and agonist-induced opening and inhibition by potent and selective antagonists.

    • Kirill D. Nadezhdin
    • , Leonor Correia
    •  & Alexander I. Sobolevsky

  • Article
    | Open Access

    Ion channels could be directly regulated by the alpha subunit of heterotrimeric G-proteins. Here, authors present the cryo-EM structure of an ion channel-Gα complex, TRPC5-Gαi3, and present functional insights into their direct interaction.

    • Jongdae Won
    • , Jinsung Kim
    •  & Hyung Ho Lee

  • Article
    | Open Access

    Small molecules targeting transient receptor potential (TRP) channels might be used to control pain. Here, Neuberger et al. report cryo-EM structures of human TRPV1 in the absence of added ligands or in the presence of the TRPV1-specific antagonist SB-366791, providing insights for the design of new promising analgesics.

    • Arthur Neuberger
    • , Mai Oda
    •  & Alexander I. Sobolevsky

  • Article
    | Open Access

    TRPV1 as a drug target suffers from side effects of hypothermia. Here, authors engineer a peptide, sRhTx, as a positive allosteric modulator of TRPV1 channel. It potentiates the activity of TRPV1 to reversibly ablate pain-sensing nerve terminals for long-lasting analgesia without changing mice body temperature.

    • Heng Zhang
    • , Jia-Jia Lin
    •  & Fan Yang

  • Article
    | Open Access

    TRPV2 is activated by temperature and cannabinoids. Here, the authors have used cryo-EM and electrophysiology to identify a cannabinoid binding site distinct from that of cannabidiol as a possible drug target for treatment of inflammation and immune-mediated diseases.

    • Liying Zhang
    • , Charlotte Simonsen
    •  & Peter M. Zygmunt

  • Article
    | Open Access

    Cryo-EM often yields multiple protein conformations within a single dataset. Using the thermal titration methods and cryo-EM, Do Hoon Kwon et al. elucidate the conformational trajectory of the TRPV1 with resiniferatoxin (RTx) bound.

    • Do Hoon Kwon
    • , Feng Zhang
    •  & Seok-Yong Lee

  • Article
    | Open Access

    A non-selective calcium channel transient receptor potential vanilloid 2 (TRPV2) is a potential drug target. Here, the authors employ cryo-electron microscopy, in silico docking, and electrophysiology to identify a binding site for an activator 2-aminoethoxydiphenyl borate (2-APB) in this channel.

    • Ruth A. Pumroy
    • , Anna D. Protopopova
    •  & Vera Y. Moiseenkova-Bell

  • Article
    | Open Access

    Hetero-oligomeric TRP-like channels such as PKD1L3/PKD2L1 play crucial roles in a range of physiological and pathophysiological processes. Here, the authors present the cryo-EM structures of a minimal functional murine PKD1L3/PKD2L1 complex in the absence and presence of calcium and further supported through structure-guided mutagenic studies, they discuss the mechanism of calcium-induced channel activation.

    • Qiang Su
    • , Mengying Chen
    •  & Yigong Shi

  • Article
    | Open Access

    Structural and functional characterization of the full-length TRPV1 channel from the thirteen-lined ground squirrel reveal the architecture of the extracellular cap domain and the intracellular C-terminus, and suggest a role of the cap domain in TRPV1 conductance and ion selectivity.

    • Kirill D. Nadezhdin
    • , Arthur Neuberger
    •  & Alexander I. Sobolevsky

  • 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

    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

    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

    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

    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

    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

    Angiotensin II type 1 receptor (AT1R)-mediated acute catecholamine release is modulated by β-arrestin. Here the authors show that β-arrestin-1 recruits the Ca2+channel TRPC3 and the PLCγ to the AT1R-β-arrestin complex, triggering G protein-independent calcium influx and catecholamine secretion.

    • Chun-Hua Liu
    • , Zheng Gong
    •  & Jin-Peng Sun

  • Article
    | Open Access

    TRPV are cation channels activated by physical and chemical stimuli. Here the authors show that nicotinamide is a soluble, endogenous agonist for orthologous TRPV channels fromC. elegans and Drosophila, unveiling a metabolic-based regulation for TRPV channel activity.

    • Awani Upadhyay
    • , Aditya Pisupati
    •  & Wendy Hanna-Rose

  • Article
    | Open Access

    TRPs are calcium-permeable channels involved in the sensing of damaging stimuli but the relationship between calcium influx and pain behaviour has been elusive. Here the authors find that the TRP channel OSM-9 functions as an ion channel in vivo in C. elegans, and establish residues that are critical for worm pain-like behaviour.

    • Amanda S. Lindy
    • , Puja K. Parekh
    •  & Wolfgang B. Liedtke

  • Article |

    Polycystic kidney disease family proteins form heteromeric complexes with transient receptor potential channel subunits of the TRPP subfamily. Yu and colleagues find that the polycystic kidney disease protein, PKD1L3, is an ion channel pore-forming subunit in the acid-sensing PKD1L3/TRPP3 complex.

    • Yong Yu
    • , Maximilian H. Ulbrich
    •  & Jian Yang

  • Article
    | Open Access

    The signalling cascade involved in lung ischaemia–reperfusion-induced oedema is poorly understood. Using knockout mice, Weissmannet al. propose a model in which reactive oxygen species production by endothelial NOX2 leads to phospholipase C-γ activation, DAG kinase inhibition and subsequent TRPC6 activation.

    • Norbert Weissmann
    • , Akylbek Sydykov
    •  & Alexander Dietrich

  • Article |

    Nitric oxide can be produced by nitric oxide synthase or by nitrite reduction, but whether the latter occurs inside cells is unknown. Here, the TRPV3 ion channel is shown to induce nitrite-dependent nitric oxide production in keratinocytes, where it has a role in thermosensory behaviour and wound healing.

    • Takashi Miyamoto
    • , Matt J. Petrus
    •  & Ardem Patapoutian

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