6WEK

Structure of cGMP-bound WT TAX-4 reconstituted in lipid nanodiscs

Summary for 6WEK

• Entry DOI: 10.2210/pdb6wek/pdb
• Related: 6WEJ
• EMDB information: 21649 21650
• Descriptor: Cyclic nucleotide-gated cation channel, CYCLIC GUANOSINE MONOPHOSPHATE, 1-PALMITOYL-2-LINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE, ... (4 entities in total)
• Functional Keywords: ion channel, vision, olfaction, phototransduction, blindness, lipid nanodiscs, membrane protein
• Biological source: Caenorhabditis elegans
• Total number of polymer chains: 4
• Total formula weight: 357679.41

Authors

Zheng, X.,Fu, Z.,Su, D.,Zhang, Y.,Li, M.,Pan, Y.,Li, H.,Li, S.,Grassucci, R.A.,Ren, Z.,Hu, Z.,Li, X.,Zhou, M.,Li, G.,Frank, J.,Yang, J. (deposition date: 2020-04-02, release date: 2020-06-03, Last modification date: 2020-07-22)

Primary citation

Zheng, X.,Fu, Z.,Su, D.,Zhang, Y.,Li, M.,Pan, Y.,Li, H.,Li, S.,Grassucci, R.A.,Ren, Z.,Hu, Z.,Li, X.,Zhou, M.,Li, G.,Frank, J.,Yang, J.
Mechanism of ligand activation of a eukaryotic cyclic nucleotide-gated channel.
Nat.Struct.Mol.Biol., 27:625-634, 2020

PubMed Abstract: 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.

PubMed: 32483338
DOI: 10.1038/s41594-020-0433-5

Experimental method

ELECTRON MICROSCOPY (2.7 Å)