6wel
From Proteopedia
Structure of cGMP-unbound F403V/V407A mutant TAX-4 reconstituted in lipid nanodiscs
Structural highlights
Function[CNG_CAEEL] Required for normal thermosensation and chemosensation sensory behavior (PubMed:8893027). Required, downstream of receptor-type guanylate cyclase gcy-9, for CO2-mediated responses in BAG neurons (PubMed:21173231). Required, downstream of receptor-type guanylate cyclase gcy-14, for alkaline pH-mediated responses in ASE-left (ASEL) neurons (PubMed:23664973). Involved in the development of ASJ sensory neuron axon during late larval stages and in the maintenance of normal axon morphology in the adult. Regulates dauer formation (PubMed:9486798). In ASI and ASJ sensory neurons, controls behavioral response to P.aeruginosa by up-regulating the transcription of daf-7, a member of the TGF-beta family (PubMed:25303524). In AWB and AWC sensory neurons, mediates the recognition of food oders which subsequently allows for the detection of preferred food sources (PubMed:25009271).[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedCyclic 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 A 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. Mechanism of ligand activation of a eukaryotic cyclic nucleotide-gated channel.,Zheng X, Fu Z, Su D, Zhang Y, Li M, Pan Y, Li H, Li S, Grassucci RA, Ren Z, Hu Z, Li X, Zhou M, Li G, Frank J, Yang J Nat Struct Mol Biol. 2020 Jun 1. pii: 10.1038/s41594-020-0433-5. doi:, 10.1038/s41594-020-0433-5. PMID:32483338[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Caeel | Large Structures | Frank, J | Fu, Z | Grassucci, R A | Hu, Z | Li, G | Li, H | Li, M | Li, S | Li, X | Pan, Y | Ren, Z | Su, D | Yang, J | Zhang, Y | Zheng, X | Zhou, M | Blindness | Cyclic nucleotide-gated channel | Ion channel | Lipid nanodisc | Membrane protein | Olfaction | Phototransduction | Vision
