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.
Structure-function elucidation of a new α-conotoxin, Lo1a, from Conus longurionis.
Lebbe EK
,
Peigneur S
,
Maiti M
,
Devi P
,
Ravichandran S
,
Lescrinier E
,
Ulens C
,
Waelkens E
,
D'Souza L
,
Herdewijn P
,
Tytgat J
.
???displayArticle.abstract???
α-Conotoxins are peptide toxins found in the venom of marine cone snails and potent antagonists of various subtypes of nicotinic acetylcholine receptors (nAChRs). nAChRs are cholinergic receptors forming ligand-gated ion channels in the plasma membranes of certain neurons and the neuromuscular junction. Because nAChRs have an important role in regulating transmitter release, cell excitability, and neuronal integration, nAChR dysfunctions have been implicated in a variety of severe pathologies such as epilepsy, myasthenic syndromes, schizophrenia, Parkinson disease, and Alzheimer disease. To expand the knowledge concerning cone snail toxins, we examined the venom of Conus longurionis. We isolated an 18-amino acid peptide named α-conotoxin Lo1a, which is active on nAChRs. To the best of our knowledge, this is the first characterization of a conotoxin from this species. The peptide was characterized by electrophysiological screening against several types of cloned nAChRs expressed in Xenopus laevis oocytes. The three-dimensional solution structure of the α-conotoxin Lo1a was determined by NMR spectroscopy. Lo1a, a member of the α4/7 family, blocks the response to acetylcholine in oocytes expressing α7 nAChRs with an IC50 of 3.24 ± 0.7 μM. Furthermore, Lo1a shows a high selectivity for neuronal versus muscle subtype nAChRs. Because Lo1a has an unusual C terminus, we designed two mutants, Lo1a-ΔD and Lo1a-RRR, to investigate the influence of the C-terminal residue. Lo1a-ΔD has a C-terminal Asp deletion, whereas in Lo1a-RRR, a triple-Arg tail replaces the Asp. They blocked the neuronal nAChR α7 with a lower IC50 value, but remarkably, both adopted affinity for the muscle subtype α1β1δε.
Alberola-Die,
Multiple inhibitory actions of lidocaine on Torpedo nicotinic acetylcholine receptors transplanted to Xenopus oocytes.
2011, Pubmed,
Xenbase
Alberola-Die,
Multiple inhibitory actions of lidocaine on Torpedo nicotinic acetylcholine receptors transplanted to Xenopus oocytes.
2011,
Pubmed
,
Xenbase
Arias,
Alpha-conotoxins.
2000,
Pubmed
Armishaw,
Rational design of alpha-conotoxin analogues targeting alpha7 nicotinic acetylcholine receptors: improved antagonistic activity by incorporation of proline derivatives.
2009,
Pubmed
Breese,
Comparison of the regional expression of nicotinic acetylcholine receptor alpha7 mRNA and [125I]-alpha-bungarotoxin binding in human postmortem brain.
1997,
Pubmed
Brejc,
Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors.
2001,
Pubmed
Cartier,
A new alpha-conotoxin which targets alpha3beta2 nicotinic acetylcholine receptors.
1996,
Pubmed
,
Xenbase
Changeux,
The TiPS lecture. The nicotinic acetylcholine receptor: an allosteric protein prototype of ligand-gated ion channels.
1990,
Pubmed
Chi,
Solution conformation of alpha-conotoxin GIC, a novel potent antagonist of alpha3beta2 nicotinic acetylcholine receptors.
2004,
Pubmed
Colquhoun,
Pharmacology of neuronal nicotinic acetylcholine receptor subtypes.
1997,
Pubmed
Cooper,
Pentameric structure and subunit stoichiometry of a neuronal nicotinic acetylcholine receptor.
1991,
Pubmed
Couturier,
A neuronal nicotinic acetylcholine receptor subunit (alpha 7) is developmentally regulated and forms a homo-oligomeric channel blocked by alpha-BTX.
1990,
Pubmed
,
Xenbase
Dowell,
Alpha-conotoxin PIA is selective for alpha6 subunit-containing nicotinic acetylcholine receptors.
2003,
Pubmed
,
Xenbase
Dutertre,
Computational approaches to understand alpha-conotoxin interactions at neuronal nicotinic receptors.
2004,
Pubmed
Dutertre,
Toxin insights into nicotinic acetylcholine receptors.
2006,
Pubmed
Everhart,
Determinants of potency on alpha-conotoxin MII, a peptide antagonist of neuronal nicotinic receptors.
2004,
Pubmed
,
Xenbase
Franco,
RegIIA: an α4/7-conotoxin from the venom of Conus regius that potently blocks α3β4 nAChRs.
2012,
Pubmed
,
Xenbase
Gold,
Pharmacogenetics of smoking cessation: role of nicotine target and metabolism genes.
2012,
Pubmed
Gotti,
Neuronal nicotinic receptors: from structure to pathology.
2004,
Pubmed
Gotti,
Human neuronal nicotinic receptors.
1997,
Pubmed
Groebe,
alpha-Conotoxins selectively inhibit one of the two acetylcholine binding sites of nicotinic receptors.
1995,
Pubmed
Grønlien,
Distinct profiles of alpha7 nAChR positive allosteric modulation revealed by structurally diverse chemotypes.
2007,
Pubmed
,
Xenbase
Hu,
The 1.1 A crystal structure of the neuronal acetylcholine receptor antagonist, alpha-conotoxin PnIA from Conus pennaceus.
1996,
Pubmed
Hu,
Crystal structure at 1.1 A resolution of alpha-conotoxin PnIB: comparison with alpha-conotoxins PnIA and GI.
1997,
Pubmed
Hwang,
Multiple-pulse mixing sequences that selectively enhance chemical exchange or cross-relaxation peaks in high-resolution NMR spectra.
1998,
Pubmed
Inserra,
Isolation and characterization of α-conotoxin LsIA with potent activity at nicotinic acetylcholine receptors.
2013,
Pubmed
Jin,
MrIC, a novel α-conotoxin agonist in the presence of PNU at endogenous α7 nicotinic acetylcholine receptors.
2014,
Pubmed
Johnson,
alpha-Conotoxin ImI exhibits subtype-specific nicotinic acetylcholine receptor blockade: preferential inhibition of homomeric alpha 7 and alpha 9 receptors.
1995,
Pubmed
,
Xenbase
Kaas,
ConoServer: updated content, knowledge, and discovery tools in the conopeptide database.
2012,
Pubmed
Keller,
The pi plate: an implant for unstable extension fractures of the distal radius in patients with osteoporotic bone.
2004,
Pubmed
Le Novère,
Molecular evolution of the nicotinic acetylcholine receptor: an example of multigene family in excitable cells.
1995,
Pubmed
Le Novère,
The diversity of subunit composition in nAChRs: evolutionary origins, physiologic and pharmacologic consequences.
2002,
Pubmed
Lewis,
Conus venom peptide pharmacology.
2012,
Pubmed
Lluisma,
Characterization of a novel psi-conotoxin from Conus parius Reeve.
2008,
Pubmed
,
Xenbase
Loughnan,
Chemical and functional identification and characterization of novel sulfated alpha-conotoxins from the cone snail Conus anemone.
2004,
Pubmed
,
Xenbase
Loughnan,
alpha-conotoxin EpI, a novel sulfated peptide from Conus episcopatus that selectively targets neuronal nicotinic acetylcholine receptors.
1998,
Pubmed
Luo,
Single-residue alteration in alpha-conotoxin PnIA switches its nAChR subtype selectivity.
1999,
Pubmed
,
Xenbase
Luo,
alpha-conotoxin AuIB selectively blocks alpha3 beta4 nicotinic acetylcholine receptors and nicotine-evoked norepinephrine release.
1998,
Pubmed
,
Xenbase
Martinez,
alpha-Conotoxin EI, a new nicotinic acetylcholine receptor antagonist with novel selectivity.
1995,
Pubmed
Marx,
NMR of conotoxins: structural features and an analysis of chemical shifts of post-translationally modified amino acids.
2006,
Pubmed
McIntosh,
A novel alpha-conotoxin, PeIA, cloned from Conus pergrandis, discriminates between rat alpha9alpha10 and alpha7 nicotinic cholinergic receptors.
2005,
Pubmed
,
Xenbase
McIntosh,
Analogs of alpha-conotoxin MII are selective for alpha6-containing nicotinic acetylcholine receptors.
2004,
Pubmed
,
Xenbase
McIntosh,
A nicotinic acetylcholine receptor ligand of unique specificity, alpha-conotoxin ImI.
1994,
Pubmed
McIntosh,
Alpha-conotoxin GIC from Conus geographus, a novel peptide antagonist of nicotinic acetylcholine receptors.
2002,
Pubmed
,
Xenbase
Nicke,
Isolation, structure, and activity of GID, a novel alpha 4/7-conotoxin with an extended N-terminal sequence.
2003,
Pubmed
,
Xenbase
Olivera,
Diversity of Conus neuropeptides.
1990,
Pubmed
Olivera,
Peptide neurotoxins from fish-hunting cone snails.
1985,
Pubmed
Park,
Solution conformation of alpha-conotoxin EI, a neuromuscular toxin specific for the alpha 1/delta subunit interface of torpedo nicotinic acetylcholine receptor.
2001,
Pubmed
Peng,
alpha4/7-conotoxin Lp1.1 is a novel antagonist of neuronal nicotinic acetylcholine receptors.
2008,
Pubmed
,
Xenbase
Peng,
Chemical synthesis and characterization of two α4/7-conotoxins.
2010,
Pubmed
,
Xenbase
Prince,
Molecular dissection of subunit interfaces in the acetylcholine receptor. Identification of residues that determine agonist selectivity.
1996,
Pubmed
Quinton,
Identification and functional characterization of a novel α-conotoxin (EIIA) from Conus ermineus.
2013,
Pubmed
Quiram,
Structural elements in alpha-conotoxin ImI essential for binding to neuronal alpha7 receptors.
1998,
Pubmed
Quiram,
Identification of residues in the neuronal alpha7 acetylcholine receptor that confer selectivity for conotoxin ImI.
1998,
Pubmed
Rezvani,
Cognitive effects of nicotine.
2001,
Pubmed
Rubboli,
Distribution of nicotinic receptors in the human hippocampus and thalamus.
1994,
Pubmed
Sacco,
Nicotinic receptor mechanisms and cognition in normal states and neuropsychiatric disorders.
2004,
Pubmed
Sandall,
A novel alpha-conotoxin identified by gene sequencing is active in suppressing the vascular response to selective stimulation of sensory nerves in vivo.
2003,
Pubmed
Schwieters,
The Xplor-NIH NMR molecular structure determination package.
2003,
Pubmed
Sine,
Molecular dissection of subunit interfaces in the acetylcholine receptor: identification of residues that determine curare selectivity.
1993,
Pubmed
Sine,
Molecular dissection of subunit interfaces in the acetylcholine receptor: identification of determinants of alpha-conotoxin M1 selectivity.
1995,
Pubmed
Sine,
Gamma- and delta-subunits regulate the affinity and the cooperativity of ligand binding to the acetylcholine receptor.
1991,
Pubmed
Spronk,
Improving the quality of protein structures derived by NMR spectroscopy.
2002,
Pubmed
Stein,
Torsion-angle molecular dynamics as a new efficient tool for NMR structure calculation.
1997,
Pubmed
Steinlein,
Nicotinic receptor channelopathies and epilepsy.
2010,
Pubmed
Talley,
Alpha-conotoxin OmIA is a potent ligand for the acetylcholine-binding protein as well as alpha3beta2 and alpha7 nicotinic acetylcholine receptors.
2006,
Pubmed
,
Xenbase
Teichert,
A uniquely selective inhibitor of the mammalian fetal neuromuscular nicotinic acetylcholine receptor.
2005,
Pubmed
,
Xenbase
Tsetlin,
Snake and snail toxins acting on nicotinic acetylcholine receptors: fundamental aspects and medical applications.
2004,
Pubmed
Van Der Haegen,
Importance of position 8 in μ-conotoxin KIIIA for voltage-gated sodium channel selectivity.
2011,
Pubmed
,
Xenbase
Wevers,
Cellular distribution of nicotinic acetylcholine receptor subunit mRNAs in the human cerebral cortex as revealed by non-isotopic in situ hybridization.
1994,
Pubmed
Whiteaker,
Discovery, synthesis, and structure activity of a highly selective alpha7 nicotinic acetylcholine receptor antagonist.
2007,
Pubmed
,
Xenbase
Yuan,
From the identification of gene organization of alpha conotoxins to the cloning of novel toxins.
2007,
Pubmed
