Proteopedia

6wek

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

Structural highlights

6wek is a 4 chain structure with sequence from Caeel. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, ,
Gene:tax-4, ZC84.2 (CAEEL)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 PubMed

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 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

  1. ↑ Hallem EA, Spencer WC, McWhirter RD, Zeller G, Henz SR, Ratsch G, Miller DM 3rd, Horvitz HR, Sternberg PW, Ringstad N. Receptor-type guanylate cyclase is required for carbon dioxide sensation by Caenorhabditis elegans. Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):254-9. doi: 10.1073/pnas.1017354108. , Epub 2010 Dec 20. PMID:21173231 doi:http://dx.doi.org/10.1073/pnas.1017354108
  2. ↑ Murayama T, Takayama J, Fujiwara M, Maruyama IN. Environmental alkalinity sensing mediated by the transmembrane guanylyl cyclase GCY-14 in C. elegans. Curr Biol. 2013 Jun 3;23(11):1007-12. doi: 10.1016/j.cub.2013.04.052. Epub 2013, May 9. PMID:23664973 doi:http://dx.doi.org/10.1016/j.cub.2013.04.052
  3. ↑ Harris G, Shen Y, Ha H, Donato A, Wallis S, Zhang X, Zhang Y. Dissecting the signaling mechanisms underlying recognition and preference of food odors. J Neurosci. 2014 Jul 9;34(28):9389-403. doi: 10.1523/JNEUROSCI.0012-14.2014. PMID:25009271 doi:http://dx.doi.org/10.1523/JNEUROSCI.0012-14.2014
  4. ↑ Meisel JD, Panda O, Mahanti P, Schroeder FC, Kim DH. Chemosensation of bacterial secondary metabolites modulates neuroendocrine signaling and behavior of C. elegans. Cell. 2014 Oct 9;159(2):267-80. doi: 10.1016/j.cell.2014.09.011. PMID:25303524 doi:http://dx.doi.org/10.1016/j.cell.2014.09.011
  5. ↑ Komatsu H, Mori I, Rhee JS, Akaike N, Ohshima Y. Mutations in a cyclic nucleotide-gated channel lead to abnormal thermosensation and chemosensation in C. elegans. Neuron. 1996 Oct;17(4):707-18. PMID:8893027
  6. ↑ Coburn CM, Mori I, Ohshima Y, Bargmann CI. A cyclic nucleotide-gated channel inhibits sensory axon outgrowth in larval and adult Caenorhabditis elegans: a distinct pathway for maintenance of sensory axon structure. Development. 1998 Jan;125(2):249-58. PMID:9486798
  7. ↑ 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. Mechanism of ligand activation of a eukaryotic cyclic nucleotide-gated channel. Nat Struct Mol Biol. 2020 Jun 1. pii: 10.1038/s41594-020-0433-5. doi:, 10.1038/s41594-020-0433-5. PMID:32483338 doi:http://dx.doi.org/10.1038/s41594-020-0433-5

6wek, resolution 2.70Å

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