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-Structure paper
タイトル | Mechanism of ligand activation of a eukaryotic cyclic nucleotide-gated channel. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 27, Issue 7, Page 625-634, Year 2020 |
掲載日 | 2020年6月1日 |
著者 | Xiangdong Zheng / Ziao Fu / Deyuan Su / Yuebin Zhang / Minghui Li / Yaping Pan / Huan Li / Shufang Li / Robert A Grassucci / Zhenning Ren / Zhengshan Hu / Xueming Li / Ming Zhou / Guohui Li / Joachim Frank / Jian Yang / |
PubMed 要旨 | Cyclic nucleotide-gated (CNG) channels convert cyclic nucleotide (CN) binding and unbinding into electrical signals in sensory receptors and neurons. The molecular conformational changes underpinning ...Cyclic nucleotide-gated (CNG) channels convert cyclic nucleotide (CN) binding and unbinding into electrical signals in sensory receptors and neurons. The molecular conformational changes underpinning ligand activation are largely undefined. We report both closed- and open-state atomic cryo-EM structures of a full-length Caenorhabditis elegans cyclic GMP-activated channel TAX-4, reconstituted in lipid nanodiscs. These structures, together with computational and functional analyses and a mutant channel structure, reveal a double-barrier hydrophobic gate formed by two S6 amino acids in the central cavity. cGMP binding produces global conformational changes that open the cavity gate located ~52 Å away but do not alter the structure of the selectivity filter-the commonly presumed activation gate. Our work provides mechanistic insights into the allosteric gating and regulation of CN-gated and nucleotide-modulated channels and CNG channel-related channelopathies. |
リンク | Nat Struct Mol Biol / PubMed:32483338 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.5 - 2.7 Å |
構造データ | EMDB-21649, PDB-6wej: EMDB-21650, PDB-6wek: EMDB-21651, PDB-6wel: |
化合物 | ChemComp-CPL: ChemComp-PX2: ChemComp-NA: ChemComp-PCG: |
由来 |
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キーワード | MEMBRANE PROTEIN / Ion channel / vision / olfaction / phototransduction / blindness / lipid nanodiscs / cyclic nucleotide-gated channel |