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CNG channel structure, function, and gating: a tale of conformational flexibility

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Abstract

Cyclic nucleotide–gated (CNG) channels are key to the signal transduction machinery of certain sensory modalities both in vertebrate and invertebrate organisms. They translate a chemical change in cyclic nucleotide concentration into an electrical signal that can spread through sensory cells. Despite CNG and voltage-gated potassium channels sharing a remarkable amino acid sequence homology and basic architectural plan, their functional properties are dramatically different. While voltage-gated potassium channels are highly selective and require membrane depolarization to open, CNG channels have low ion selectivity and are not very sensitive to voltage. In the last few years, many high-resolution structures of intact CNG channels have been released. This wealth of new structural information has provided enormous progress toward the understanding of the molecular mechanisms and driving forces underpinning CNG channel activation. In this review, we report on the current understanding and controversies surrounding the gating mechanism in CNG channels, as well as the deep intertwining existing between gating, the ion permeation process, and its modulation by membrane voltage. While the existence of this powerful coupling was recognized many decades ago, its direct structural demonstration, and ties to the CNG channel inherent pore flexibility, is a recent achievement.

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Authors and Affiliations

  1. Structural Biology Laboratory, Elettra-Sincrotrone Trieste S.C.p.A., Basovizza, Trieste, Italy

    Luisa Maria Rosaria Napolitano

  2. International School for Advanced Studies (SISSA), via Bonomea 265, 34136, Trieste, Italy

    Vincent Torre

  3. Institute of Materials (IOM-CNR), Area Science Park, 34149, BasovizzaTrieste, Italy

    Vincent Torre

  4. Institute of Systems Medicine Suzhou, SISSA-ISM Labs, Suzhou, Joint, China

    Vincent Torre

  5. Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, Japan

    Arin Marchesi

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  1. Luisa Maria Rosaria Napolitano
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  2. Vincent Torre
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  3. Arin Marchesi
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Correspondence to Arin Marchesi.

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This article is part of the special issue on Function and Dysfunction in Vertebrate Photoreceptor Cells in Pflügers Archiv—European Journal of Physiology

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Napolitano, L.M.R., Torre, V. & Marchesi, A. CNG channel structure, function, and gating: a tale of conformational flexibility. Pflugers Arch - Eur J Physiol 473, 1423–1435 (2021). https://doi.org/10.1007/s00424-021-02610-6

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