Ligand-gated ion channels articles within Nature Communications

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  • Article
    | Open Access

    Despite essential roles in adult nervous systems, how heteromeric Cys-loop receptors work is unclear in the absence of an open state structure. Here, the authors report closed/open state structures and functional experiments, detailing an asymmetric gating mechanism driven by differing contributions from each subunit type.

    • Xiaofen Liu
    •  & Weiwei Wang
  • Article
    | Open Access

    P2X3 activation requires tightening the inner pocket of the head domain (IP-HD) following ATP binding. Here the authors demonstrate that targeting the IP-HD with allosteric small molecules presents a potential strategy for the development of therapeutics for refractory chronic cough without taste abnormalities.

    • Chang-Run Guo
    • , Zhong-Zhe Zhang
    •  & Ye Yu
  • Article
    | Open Access

    Ligand-gated ion channels are activated/opened by agonists. Tessier et al. show that agonists can inhibit the inhibition of intrinsic basal activity, and thus that activation may instead be the manifestation of a derepression mechanism.

    • Christian J. G. Tessier
    • , Johnathon R. Emlaw
    •  & Corrie J. B. daCosta
  • Article
    | Open Access

    AMPA receptors associated with TARP subunits enable the development of selective AMPA receptor drugs. Here, the authors provide cryo-EM structures of receptors bound to three TARP-γ8 selective drugs, and reveal bifunctionality of one ligand.

    • Danyang Zhang
    • , Remigijus Lape
    •  & Ingo H. Greger
  • Article
    | Open Access

    Pentameric ligand-gated ion channels are modulated by anionic phospholipids. Here, by capturing an open-channel conformation of ELIC, the authors demonstrate the structural details of channel activation and a leaflet-specific mechanism for modulation by phosphatidylglycerol.

    • John T. Petroff II
    • , Noah M. Dietzen
    •  & Wayland W. L. Cheng
  • Article
    | Open Access

    TMEM16F is a dual ion channel and lipid scramblase that is involved in blood coagulation and cell fusion. Here, authors elucidate how the protein is activated by Ca2+ to accomplish both functions in a single protein conformation.

    • Melanie Arndt
    • , Carolina Alvadia
    •  & Raimund Dutzler
  • Article
    | Open Access

    The intracellular domain (ICD) of Cys-loop receptors mediates many of their functions, but no complete structure of a Cys-loop receptor ICD is available to date. Here, the authors combine NMR and ESR spectroscopy to determine the full-length ICD structures of the human α7 nicotinic acetylcholine receptor (α7nAChR).

    • Vasyl Bondarenko
    • , Marta M. Wells
    •  & Pei Tang
  • Article
    | Open Access

    AMPA glutamate receptors, mediate the majority of excitatory signaling in the brain. Here the authors show how the auxiliary subunit TARP-γ8 shapes gating kinetics, ion conductance and rectification properties of the heteromeric GluA1/2 AMPA receptor.

    • Beatriz Herguedas
    • , Bianka K. Kohegyi
    •  & Ingo H. Greger
  • Article
    | Open Access

    GABAA receptors (GABAARs) cause inhibition in the brain by functioning as heteropentamers formed from multiple subunit types. Here, the authors demonstrate that receptors incorporating β3 subunits can spontaneously gate, which is modulated by protein kinases and neurosteroids to affect tonic inhibition.

    • Craig A. Sexton
    • , Reka Penzinger
    •  & Trevor G. Smart
  • Article
    | Open Access

    The analysis of AMPA-type glutamate receptor (AMPAR) trafficking is essential for understanding molecular mechanisms of learning and memory, but the analytical tools are currently limited. Here, the authors report a method that combines affinity-based receptor labeling and bioorthogonal click chemistry to quantify AMPAR distribution and trafficking under physiological conditions.

    • Kento Ojima
    • , Kazuki Shiraiwa
    •  & Shigeki Kiyonaka
  • Article
    | Open Access

    GABAA receptors mediate most inhibitory synaptic transmission in the brain. Here authors used concatemeric α1β2γ2 GABAA receptors to introduce gain-of-desensitization mutations one subunit at a time, revealing non-concerted rearrangements with a key contribution of the γ2 subunit during desensitization.

    • Marc Gielen
    • , Nathalie Barilone
    •  & Pierre-Jean Corringer
  • 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

    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

    Adult and fetal nicotinic acetylcholine receptors (AChRs) have different functional requirements and affinity for ACh. Here, the authors use molecular dynamics and electrophysiology to investigate this affinity, and identify four amino acids that when swapped exchange function between adult and fetal AChRs.

    • Tapan Kumar Nayak
    • , Srirupa Chakraborty
    •  & Anthony Auerbach
  • Article |

    Alcohols and anaesthetics exert their effects by potentiating ligand-gated ion channels. Here, the authors determine crystal structures of a bacterial ligand-gated ion channel in the presence of alcohols and anaesthetics, and describe a structural mechanism for stabilization of the open form of the channel.

    • Ludovic Sauguet
    • , Rebecca J. Howard
    •  & Marc Delarue
  • Article |

    The design of chemical photoswitches could potentially lead to the development of novel therapeutics that regulates neurotransmission. In this study, a light-sensitive modified derivative of propofol is shown to activate GABAA receptors in Xenopusoocytes, rat ganglion cells and mouse cerebellar slices.

    • Lan Yue
    • , Michal Pawlowski
    •  & David R. Pepperberg
  • Article
    | Open Access

    The pentameric ligand gated ion channel fromErwinia chrysanthemi(ELIC) is similar in structure to the nicotinic acetylcholine receptor, a member of the Cys-loop receptor family. This study reports the crystal structure of ELIC bound to acetylcholine and shows that acetylcholine is a competitive antagonist of ELIC.

    • Jianjun Pan
    • , Qiang Chen
    •  & Pei Tang
  • Article |

    In non-NMDA glutamate receptors, intersubunit contacts within agonist binding domains affect functional desensitization. Now, NMDA receptor activation, but not desensitization, is shown to involve rearrangements at the heterodimer interface, suggesting that the intersubunit contacts of NMDA and non-NMDA receptors may have distinct functional roles.

    • William F. Borschel
    • , Swetha E. Murthy
    •  & Gabriela K. Popescu
  • Article |

    N-methyl-D-aspartate receptors mediate excitatory synaptic transmission, and those containing GluN2D subunits have an unusually long deactivation time. Vance et al. show that the conformational variability of the ligand-binding domain and the structure of the activating ligand influence deactivation time.

    • Katie M. Vance
    • , Noriko Simorowski
    •  & Hiro Furukawa
  • Article |

    NMDA receptors are complexes of NR1 and NR2 subunits that mediate excitatory synaptic transmission and have roles in neurological disorders. Here, a subunit-selective potentiator of NMDA receptors is identified, which may allow the evaluation of the functional roles of individual NMDA receptor subunits.

    • Praseeda Mullasseril
    • , Kasper B. Hansen
    •  & Stephen F. Traynelis
  • Article
    | Open Access

    A recent X-ray structure revealed the closed state of a P2X receptor ion channel. Here, Li and colleagues probe the structural rearrangements that take place during channel opening by measuring the effects of covalent modification of engineered cysteines.

    • Mufeng Li
    • , Toshimitsu Kawate
    •  & Kenton J. Swartz