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TitleMechanism of ligand activation of a eukaryotic cyclic nucleotide-gated channel.
Journal, issue, pagesNat Struct Mol Biol, Vol. 27, Issue 7, Page 625-634, Year 2020
Publish dateJun 1, 2020
AuthorsXiangdong 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 AbstractCyclic 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.
External linksNat Struct Mol Biol / PubMed:32483338 / PubMed Central
MethodsEM (single particle)
Resolution2.5 - 2.7 Å
Structure data

21649

6wej

EMDB-21649, PDB-6wej:
Structure of cGMP-unbound WT TAX-4 reconstituted in lipid nanodiscs
Method: EM (single particle) / Resolution: 2.6 Å

21650

6wek

EMDB-21650, PDB-6wek:
Structure of cGMP-bound WT TAX-4 reconstituted in lipid nanodiscs
Method: EM (single particle) / Resolution: 2.7 Å

21651

6wel

EMDB-21651, PDB-6wel:
Structure of cGMP-unbound F403V/V407A mutant TAX-4 reconstituted in lipid nanodiscs
Method: EM (single particle) / Resolution: 2.5 Å

Chemicals

ChemComp-CPL:
1-PALMITOYL-2-LINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / phospholipid*YM

ChemComp-PX2:
1,2-DILAUROYL-SN-GLYCERO-3-PHOSPHATE

ChemComp-NA:
Unknown entry

ChemComp-PCG:
CYCLIC GUANOSINE MONOPHOSPHATE

Source
  • caenorhabditis elegans (invertebrata)
KeywordsMEMBRANE PROTEIN / Ion channel / vision / olfaction / phototransduction / blindness / lipid nanodiscs / cyclic nucleotide-gated channel

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