title: Structure of a eukaryotic cyclic-nucleotide-gated channel.
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.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
authors.forename: Minghui
authors.initials: M
authors.lastname: Li
authors.affiliation: Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Chinese Academy of Sciences, Kunming 650223, China.|Key Laboratory of Bioactive Peptides of Yunnan Province, Chinese Academy of Sciences, Kunming 650223, China.|Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Michailidis
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Chinese Academy of Sciences, Kunming 650223, China.|Key Laboratory of Bioactive Peptides of Yunnan Province, Chinese Academy of Sciences, Kunming 650223, China.|Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Chinese Academy of Sciences, Kunming 650223, China.|Key Laboratory of Bioactive Peptides of Yunnan Province, Chinese Academy of Sciences, Kunming 650223, China.|Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China.
authors.forename: Deyuan
authors.initials: D
authors.lastname: Su
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Chinese Academy of Sciences, Kunming 650223, China.|Key Laboratory of Bioactive Peptides of Yunnan Province, Chinese Academy of Sciences, Kunming 650223, China.|Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Li
authors.affiliation: Beijing Advanced Innovation Center for Structural Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xueming
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA.|Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences, Chinese Academy of Sciences, Kunming 650223, China.|Key Laboratory of Bioactive Peptides of Yunnan Province, Chinese Academy of Sciences, Kunming 650223, China.|Ion Channel Research and Drug Development Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D006152:Cyclic GMP / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D004553:Electric Conductivity; D018698:Glutamic Acid / Q000737:chemistry / Q000378:metabolism; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure*; D008954:Models, Biological; D008958:Models, Molecular; D000072417:Protein Domains
chemical_list: D029742:Caenorhabditis elegans Proteins; D054815:Cyclic Nucleotide-Gated Cation Channels; D007473:Ion Channels; C102184:tax-4 protein, C elegans; D018698:Glutamic Acid; D006152:Cyclic GMP