6WEL

Structure of cGMP-unbound F403V/V407A mutant TAX-4 reconstituted in lipid nanodiscs

Summary for 6WEL

• Entry DOI: 10.2210/pdb6wel/pdb
• Related: 6WEJ 6WEK
• EMDB information: 21649 21650 21651
• Descriptor: Cyclic nucleotide-gated cation channel, 1-PALMITOYL-2-LINOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE, 1,2-DILAUROYL-SN-GLYCERO-3-PHOSPHATE, ... (4 entities in total)
• Functional Keywords: ion channel, vision, olfaction, phototransduction, blindness, cyclic nucleotide-gated channel, lipid nanodiscs, membrane protein
• Biological source: Caenorhabditis elegans
• Total number of polymer chains: 4
• Total formula weight: 361192.13

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: 2024-10-23)

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 (2.5 Å)