Structure of a eukaryotic cyclic-nucleotide-gated channel

Nature. 2017 Feb 2;542(7639):60-65. doi: 10.1038/nature20819. Epub 2017 Jan 18.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans Proteins / chemistry*
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans Proteins / ultrastructure*
  • Caenorhabditis elegans* / chemistry
  • Caenorhabditis elegans* / ultrastructure
  • Cryoelectron Microscopy*
  • Cyclic GMP / metabolism
  • Cyclic Nucleotide-Gated Cation Channels / chemistry*
  • Cyclic Nucleotide-Gated Cation Channels / metabolism
  • Cyclic Nucleotide-Gated Cation Channels / ultrastructure*
  • Electric Conductivity
  • Glutamic Acid / chemistry
  • Glutamic Acid / metabolism
  • Ion Channel Gating
  • Ion Channels / chemistry*
  • Ion Channels / metabolism
  • Ion Channels / ultrastructure*
  • Models, Biological
  • Models, Molecular
  • Protein Domains

Substances

  • Caenorhabditis elegans Proteins
  • Cyclic Nucleotide-Gated Cation Channels
  • Ion Channels
  • tax-4 protein, C elegans
  • Glutamic Acid
  • Cyclic GMP