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

Structure of a eukaryotic cyclic-nucleotide-gated channel.

Li M1, Zhou X2, Wang S3,4,5,6, Michailidis I1, Gong Y3,4,5, Su D3,4,5,6, Li H3,4,5,6, Li X2, Yang J1,3,4,5.

Author information

1
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
2
Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
3
Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Chinese Academy of Sciences, Kunming 650223, China.
4
Key Laboratory of Bioactive Peptides of Yunnan Province, Chinese Academy of Sciences, Kunming 650223, China.
5
Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
6
Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China.

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.

PMID:
28099415
PMCID:
PMC5783306
DOI:
10.1038/nature20819
[Indexed for MEDLINE]
Free PMC Article

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