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Structure of a eukaryotic cyclic-nucleotide-gated channel.

Li M, Zhou X, Wang S, Michailidis I, Gong Y, Su D, Li H, Li X, Yang J
Nature 542 60-65 (2017)
Cited: 90 times
EuropePMC logo PMID: 28099415

Abstract

Cyclic-nucleotide-gated channels are essential for vision and olfaction. They belong to the voltage-gated ion channel superfamily but their activities are controlled by intracellular cyclic nucleotides instead of transmembrane voltage. Here we report a 3.5-Å-resolution single-particle electron cryo-microscopy structure of a cyclic-nucleotide-gated channel from Caenorhabditis elegans in the cyclic guanosine monophosphate (cGMP)-bound open state. The channel has an unusual voltage-sensor-like domain, accounting for its deficient voltage dependence. A carboxy-terminal linker connecting S6 and the cyclic-nucleotide-binding domain interacts directly with both the voltage-sensor-like domain and the pore domain, forming a gating ring that couples conformational changes triggered by cyclic nucleotide binding to the gate. The selectivity filter is lined by the carboxylate side chains of a functionally important glutamate and three rings of backbone carbonyls. This structure provides a new framework for understanding mechanisms of ion permeation, gating and channelopathy of cyclic-nucleotide-gated channels and cyclic nucleotide modulation of related channels.

Reviews - 5h3o mentioned but not cited (3)

  1. Structural insights into the mechanisms of CNBD channel function. James ZM, Zagotta WN. J Gen Physiol 150 225-244 (2018)
  2. Retinal Cyclic Nucleotide-Gated Channels: From Pathophysiology to Therapy. Michalakis S, Becirovic E, Biel M. Int J Mol Sci 19 E749 (2018)
  3. Structural basis of properties, mechanisms, and channelopathy of cyclic nucleotide-gated channels. Hu Z, Yang J. Channels (Austin) 17 2273165 (2023)

Articles - 5h3o mentioned but not cited (15)



Reviews citing this publication (17)

  1. Cryo-EM in drug discovery: achievements, limitations and prospects. Renaud JP, Chari A, Ciferri C, Liu WT, Rémigy HW, Stark H, Wiesmann C. Nat Rev Drug Discov 17 471-492 (2018)
  2. Evolution and Structural Characteristics of Plant Voltage-Gated K+ Channels. Jegla T, Busey G, Assmann SM. Plant Cell 30 2898-2909 (2018)
  3. The extraordinary AFD thermosensor of C. elegans. Goodman MB, Sengupta P. Pflugers Arch 470 839-849 (2018)
  4. New Structures and Gating of Voltage-Dependent Potassium (Kv) Channels and Their Relatives: A Multi-Domain and Dynamic Question. Barros F, Pardo LA, Domínguez P, Sierra LM, de la Peña P. Int J Mol Sci 20 E248 (2019)
  5. The EAG Voltage-Dependent K+ Channel Subfamily: Similarities and Differences in Structural Organization and Gating. Barros F, de la Peña P, Domínguez P, Sierra LM, Pardo LA. Front Pharmacol 11 411 (2020)
  6. Ligand-Binding Sites in Vanilloid-Subtype TRP Channels. Yelshanskaya MV, Sobolevsky AI. Front Pharmacol 13 900623 (2022)
  7. Structure and function of the calcium-selective TRP channel TRPV6. Yelshanskaya MV, Nadezhdin KD, Kurnikova MG, Sobolevsky AI. J Physiol 599 2673-2697 (2021)
  8. CNG channel structure, function, and gating: a tale of conformational flexibility. Napolitano LMR, Torre V, Marchesi A. Pflugers Arch 473 1423-1435 (2021)
  9. Never at rest: insights into the conformational dynamics of ion channels from cryo-electron microscopy. Lau C, Hunter MJ, Stewart A, Perozo E, Vandenberg JI. J Physiol 596 1107-1119 (2018)
  10. hERG Function in Light of Structure. Robertson GA, Morais-Cabral JH. Biophys J 118 790-797 (2020)
  11. The bare necessities of plant K+ channel regulation. Lefoulon C. Plant Physiol 187 2092-2109 (2021)
  12. Gating and regulation of KCNH (ERG, EAG, and ELK) channels by intracellular domains. Codding SJ, Johnson AA, Trudeau MC. Channels (Austin) 14 294-309 (2020)
  13. Biology, Pathobiology and Gene Therapy of CNG Channel-Related Retinopathies. Gerhardt MJ, Priglinger SG, Biel M, Michalakis S. Biomedicines 11 269 (2023)
  14. Insights into channel dysfunction from modelling and molecular dynamics simulations. Musgaard M, Paramo T, Domicevica L, Andersen OJ, Biggin PC. Neuropharmacology 132 20-30 (2018)
  15. X-ray crystallography of TRP channels. Singh AK, McGoldrick LL, Saotome K, Sobolevsky AI. Channels (Austin) 12 137-152 (2018)
  16. To Be or Not to Be an Ion Channel: Cryo-EM Structures Have a Say. Chen GL, Li J, Zhang J, Zeng B. Cells 12 1870 (2023)
  17. Structural Plasticity of the Selectivity Filter in Cation Channels. Hendriks K, Öster C, Lange A. Front Physiol 12 792958 (2021)

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