Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2020 Jun 16;11724:13437-13446. doi: 10.1073/pnas.1922701117.
Show Gene links
Show Anatomy links
Structural basis for allosteric transitions of a multidomain pentameric ligand-gated ion channel.
Hu H
,
Howard RJ
,
Bastolla U
,
Lindahl E
,
Delarue M
.
???displayArticle.abstract???
Pentameric ligand-gated ion channels (pLGICs) are allosteric receptors that mediate rapid electrochemical signal transduction in the animal nervous system through the opening of an ion pore upon binding of neurotransmitters. Orthologs have been found and characterized in prokaryotes and they display highly similar structure-function relationships to eukaryotic pLGICs; however, they often encode greater architectural diversity involving additional amino-terminal domains (NTDs). Here we report structural, functional, and normal-mode analysis of two conformational states of a multidomain pLGIC, called DeCLIC, from a Desulfofustis deltaproteobacterium, including a periplasmic NTD fused to the conventional ligand-binding domain (LBD). X-ray structure determination revealed an NTD consisting of two jelly-roll domains interacting across each subunit interface. Binding of Ca2+ at the LBD subunit interface was associated with a closed transmembrane pore, with resolved monovalent cations intracellular to the hydrophobic gate. Accordingly, DeCLIC-injected oocytes conducted currents only upon depletion of extracellular Ca2+; these were insensitive to quaternary ammonium block. Furthermore, DeCLIC crystallized in the absence of Ca2+ with a wide-open pore and remodeled periplasmic domains, including increased contacts between the NTD and classic LBD agonist-binding sites. Functional, structural, and dynamical properties of DeCLIC paralleled those of sTeLIC, a pLGIC from another symbiotic prokaryote. Based on these DeCLIC structures, we would reclassify the previous structure of bacterial ELIC (the first high-resolution structure of a pLGIC) as a "locally closed" conformation. Taken together, structures of DeCLIC in multiple conformations illustrate dramatic conformational state transitions and diverse regulatory mechanisms available to ion channels in pLGICs, particularly involving Ca2+ modulation and periplasmic NTDs.
Adams,
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
2010, Pubmed
Adams,
PHENIX: a comprehensive Python-based system for macromolecular structure solution.
2010,
Pubmed
Alfayate,
Predicted dynamical couplings of protein residues characterize catalysis, transport and allostery.
2019,
Pubmed
Althoff,
X-ray structures of GluCl in apo states reveal a gating mechanism of Cys-loop receptors.
2014,
Pubmed
Ashkenazy,
ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules.
2016,
Pubmed
Baenziger,
3D structure and allosteric modulation of the transmembrane domain of pentameric ligand-gated ion channels.
2011,
Pubmed
Basak,
Cryo-EM reveals two distinct serotonin-bound conformations of full-length 5-HT3A receptor.
2018,
Pubmed
,
Xenbase
Basak,
Crystal structure and dynamics of a lipid-induced potential desensitized-state of a pentameric ligand-gated channel.
2017,
Pubmed
Blanc,
Refinement of severely incomplete structures with maximum likelihood in BUSTER-TNT.
2004,
Pubmed
Bocquet,
A prokaryotic proton-gated ion channel from the nicotinic acetylcholine receptor family.
2007,
Pubmed
,
Xenbase
Bocquet,
X-ray structure of a pentameric ligand-gated ion channel in an apparently open conformation.
2009,
Pubmed
Briegel,
Structure of bacterial cytoplasmic chemoreceptor arrays and implications for chemotactic signaling.
2014,
Pubmed
Changeux,
Use of a snake venom toxin to characterize the cholinergic receptor protein.
1970,
Pubmed
Corringer,
Structure and pharmacology of pentameric receptor channels: from bacteria to brain.
2012,
Pubmed
Du,
Glycine receptor mechanism elucidated by electron cryo-microscopy.
2015,
Pubmed
Emsley,
Features and development of Coot.
2010,
Pubmed
Fourati,
Structural Basis for a Bimodal Allosteric Mechanism of General Anesthetic Modulation in Pentameric Ligand-Gated Ion Channels.
2018,
Pubmed
,
Xenbase
Fritschy,
Gephyrin: where do we stand, where do we go?
2008,
Pubmed
Gharpure,
Agonist Selectivity and Ion Permeation in the α3β4 Ganglionic Nicotinic Receptor.
2019,
Pubmed
Gonzalez-Gutierrez,
Gating of the proton-gated ion channel from Gloeobacter violaceus at pH 4 as revealed by X-ray crystallography.
2013,
Pubmed
Gonzalez-Gutierrez,
Chasing the open-state structure of pentameric ligand-gated ion channels.
2017,
Pubmed
Gonzalez-Gutierrez,
Mutations that stabilize the open state of the Erwinia chrisanthemi ligand-gated ion channel fail to change the conformation of the pore domain in crystals.
2012,
Pubmed
,
Xenbase
Gonzalez-Gutierrez,
The atypical cation-conduction and gating properties of ELIC underscore the marked functional versatility of the pentameric ligand-gated ion-channel fold.
2015,
Pubmed
Hassaine,
X-ray structure of the mouse serotonin 5-HT3 receptor.
2014,
Pubmed
Heusser,
Functional characterization of neurotransmitter activation and modulation in a nematode model ligand-gated ion channel.
2016,
Pubmed
,
Xenbase
Hibbs,
Principles of activation and permeation in an anion-selective Cys-loop receptor.
2011,
Pubmed
Hilf,
X-ray structure of a prokaryotic pentameric ligand-gated ion channel.
2008,
Pubmed
Hilf,
Structure of a potentially open state of a proton-activated pentameric ligand-gated ion channel.
2009,
Pubmed
Holm,
Dali server update.
2016,
Pubmed
Hu,
Crystal structures of a pentameric ion channel gated by alkaline pH show a widely open pore and identify a cavity for modulation.
2018,
Pubmed
Hu,
Electrostatics, proton sensor, and networks governing the gating transition in GLIC, a proton-gated pentameric ion channel.
2018,
Pubmed
Huang,
Crystal structure of human glycine receptor-α3 bound to antagonist strychnine.
2015,
Pubmed
Huang,
Crystal Structures of Human GlyRα3 Bound to Ivermectin.
2017,
Pubmed
Jaiteh,
Evolution of Pentameric Ligand-Gated Ion Channels: Pro-Loop Receptors.
2016,
Pubmed
Jones,
Direct measurement of free Ca(2+) shows different regulation of Ca(2+) between the periplasm and the cytosol of Escherichia coli.
2002,
Pubmed
Kabsch,
Integration, scaling, space-group assignment and post-refinement.
2010,
Pubmed
Krupovic,
Virus evolution: how far does the double beta-barrel viral lineage extend?
2008,
Pubmed
Laverty,
Cryo-EM structure of the human α1β3γ2 GABAA receptor in a lipid bilayer.
2019,
Pubmed
McCoy,
Phaser crystallographic software.
2007,
Pubmed
Mendez,
Torsional network model: normal modes in torsion angle space better correlate with conformation changes in proteins.
2010,
Pubmed
Miller,
Crystal structure of a human GABAA receptor.
2014,
Pubmed
Morales-Perez,
X-ray structure of the human α4β2 nicotinic receptor.
2016,
Pubmed
Neff,
Postsynaptic scaffolds for nicotinic receptors on neurons.
2009,
Pubmed
O'Hara,
The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins.
1993,
Pubmed
Phulera,
Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor in complex with GABA.
2018,
Pubmed
Plested,
Structural mechanisms of activation and desensitization in neurotransmitter-gated ion channels.
2016,
Pubmed
Polovinkin,
Conformational transitions of the serotonin 5-HT3 receptor.
2018,
Pubmed
Prevost,
A locally closed conformation of a bacterial pentameric proton-gated ion channel.
2012,
Pubmed
Ruan,
Structural titration of receptor ion channel GLIC gating by HS-AFM.
2018,
Pubmed
Sauguet,
Crystallographic studies of pharmacological sites in pentameric ligand-gated ion channels.
2015,
Pubmed
Sauguet,
Structural basis for ion permeation mechanism in pentameric ligand-gated ion channels.
2013,
Pubmed
,
Xenbase
Sauguet,
Structural basis for potentiation by alcohols and anaesthetics in a ligand-gated ion channel.
2013,
Pubmed
Sauguet,
Crystal structures of a pentameric ligand-gated ion channel provide a mechanism for activation.
2014,
Pubmed
,
Xenbase
Sine,
On the origin of ion selectivity in the Cys-loop receptor family.
2010,
Pubmed
Spurny,
Pentameric ligand-gated ion channel ELIC is activated by GABA and modulated by benzodiazepines.
2012,
Pubmed
,
Xenbase
Tasneem,
Identification of the prokaryotic ligand-gated ion channels and their implications for the mechanisms and origins of animal Cys-loop ion channels.
2005,
Pubmed
Venkatachalan,
Optimized expression vector for ion channel studies in Xenopus oocytes and mammalian cells using alfalfa mosaic virus.
2007,
Pubmed
,
Xenbase
Wilbanks,
Microscale sulfur cycling in the phototrophic pink berry consortia of the Sippewissett Salt Marsh.
2014,
Pubmed
Winn,
Overview of the CCP4 suite and current developments.
2011,
Pubmed
Zhu,
Structure of a human synaptic GABAA receptor.
2018,
Pubmed
Zhu,
Allosteric modulators of NMDA receptors: multiple sites and mechanisms.
2015,
Pubmed
Zimmermann,
Inhibition of the prokaryotic pentameric ligand-gated ion channel ELIC by divalent cations.
2012,
Pubmed
,
Xenbase