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

Pflugers Arch. 2021 Sep;473(9):1423-1435. doi: 10.1007/s00424-021-02610-6. Epub 2021 Aug 6.

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.

Keywords: CNG channels; Gating; Ion channel evolution; Ion channel structure; Ion permeation.

Publication types

  • Review

MeSH terms

  • Animals
  • Cyclic Nucleotide-Gated Cation Channels / chemistry*
  • Cyclic Nucleotide-Gated Cation Channels / physiology*
  • Humans
  • Ion Channel Gating / physiology*
  • Protein Conformation
  • Protein Structure, Secondary
  • Retinal Rod Photoreceptor Cells / chemistry
  • Retinal Rod Photoreceptor Cells / physiology
  • Signal Transduction / physiology

Substances

  • Cyclic Nucleotide-Gated Cation Channels