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.
J Biol Chem
2011 Mar 25;28612:10618-27. doi: 10.1074/jbc.M110.189100.
Show Gene links
Show Anatomy links
NMR structure and action on nicotinic acetylcholine receptors of water-soluble domain of human LYNX1.
Lyukmanova EN
,
Shenkarev ZO
,
Shulepko MA
,
Mineev KS
,
D'Hoedt D
,
Kasheverov IE
,
Filkin SY
,
Krivolapova AP
,
Janickova H
,
Dolezal V
,
Dolgikh DA
,
Arseniev AS
,
Bertrand D
,
Tsetlin VI
,
Kirpichnikov MP
.
???displayArticle.abstract???
Discovery of proteins expressed in the central nervous system sharing the three-finger structure with snake α-neurotoxins provoked much interest to their role in brain functions. Prototoxin LYNX1, having homology both to Ly6 proteins and three-finger neurotoxins, is the first identified member of this family membrane-tethered by a GPI anchor, which considerably complicates in vitro studies. We report for the first time the NMR spatial structure for the water-soluble domain of human LYNX1 lacking a GPI anchor (ws-LYNX1) and its concentration-dependent activity on nicotinic acetylcholine receptors (nAChRs). At 5-30 μM, ws-LYNX1 competed with (125)I-α-bungarotoxin for binding to the acetylcholine-binding proteins (AChBPs) and to Torpedo nAChR. Exposure of Xenopus oocytes expressing α7 nAChRs to 1 μM ws-LYNX1 enhanced the response to acetylcholine, but no effect was detected on α4β2 and α3β2 nAChRs. Increasing ws-LYNX1 concentration to 10 μM caused a modest inhibition of these three nAChR subtypes. A common feature for ws-LYNX1 and LYNX1 is a decrease of nAChR sensitivity to high concentrations of acetylcholine. NMR and functional analysis both demonstrate that ws-LYNX1 is an appropriate model to shed light on the mechanism of LYNX1 action. Computer modeling, based on ws-LYNX1 NMR structure and AChBP x-ray structure, revealed a possible mode of ws-LYNX1 binding.
Antil-Delbeke,
Molecular determinants by which a long chain toxin from snake venom interacts with the neuronal alpha 7-nicotinic acetylcholine receptor.
2000, Pubmed
Antil-Delbeke,
Molecular determinants by which a long chain toxin from snake venom interacts with the neuronal alpha 7-nicotinic acetylcholine receptor.
2000,
Pubmed
Arredondo,
SLURP-2: A novel cholinergic signaling peptide in human mucocutaneous epithelium.
2006,
Pubmed
Bax,
Measurement of homo- and heteronuclear J couplings from quantitative J correlation.
1994,
Pubmed
Betzel,
The refined crystal structure of alpha-cobratoxin from Naja naja siamensis at 2.4-A resolution.
1991,
Pubmed
Bourne,
Crystal structure of a Cbtx-AChBP complex reveals essential interactions between snake alpha-neurotoxins and nicotinic receptors.
2005,
Pubmed
Celie,
Crystal structure of nicotinic acetylcholine receptor homolog AChBP in complex with an alpha-conotoxin PnIA variant.
2005,
Pubmed
,
Xenbase
Celie,
Nicotine and carbamylcholine binding to nicotinic acetylcholine receptors as studied in AChBP crystal structures.
2004,
Pubmed
Chimienti,
Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda.
2003,
Pubmed
,
Xenbase
Delaglio,
Measurement of homonuclear proton couplings from regular 2D COSY spectra.
2001,
Pubmed
Dellisanti,
Crystal structure of the extracellular domain of nAChR alpha1 bound to alpha-bungarotoxin at 1.94 A resolution.
2007,
Pubmed
Ellison,
Alpha-conotoxins ImI and ImII. Similar alpha 7 nicotinic receptor antagonists act at different sites.
2003,
Pubmed
Fletcher,
Structure of a soluble, glycosylated form of the human complement regulatory protein CD59.
1994,
Pubmed
Güntert,
Automated NMR structure calculation with CYANA.
2004,
Pubmed
Hogg,
An automated system for intracellular and intranuclear injection.
2008,
Pubmed
,
Xenbase
Hruska,
Prostate stem cell antigen is an endogenous lynx1-like prototoxin that antagonizes alpha7-containing nicotinic receptors and prevents programmed cell death of parasympathetic neurons.
2009,
Pubmed
Ibañez-Tallon,
Tethering naturally occurring peptide toxins for cell-autonomous modulation of ion channels and receptors in vivo.
2004,
Pubmed
,
Xenbase
Ibañez-Tallon,
Novel modulation of neuronal nicotinic acetylcholine receptors by association with the endogenous prototoxin lynx1.
2002,
Pubmed
,
Xenbase
Jakubík,
Differences in kinetics of xanomeline binding and selectivity of activation of G proteins at M(1) and M(2) muscarinic acetylcholine receptors.
2006,
Pubmed
Kasheverov,
Interaction of alpha-conotoxin ImII and its analogs with nicotinic receptors and acetylcholine-binding proteins: additional binding sites on Torpedo receptor.
2009,
Pubmed
,
Xenbase
Leath,
High-resolution structures of bacterially expressed soluble human CD59.
2007,
Pubmed
Liu,
Identification of two Lynx proteins in Nilaparvata lugens and the modulation on insect nicotinic acetylcholine receptors.
2009,
Pubmed
,
Xenbase
Liukmanova,
[The in vitro production of three-finger neurotoxins from snake venoms with a high abundance of disulfide bonds. Problems and their solutions].
2010,
Pubmed
Lomholt,
Intact and cleaved forms of the urokinase receptor enhance discrimination of cancer from non-malignant conditions in patients presenting with symptoms related to colorectal cancer.
2009,
Pubmed
Lyukmanova,
Bacterial expression, NMR, and electrophysiology analysis of chimeric short/long-chain alpha-neurotoxins acting on neuronal nicotinic receptors.
2007,
Pubmed
,
Xenbase
Lyukmanova,
Bacterial production and refolding from inclusion bodies of a "weak" toxin, a disulfide rich protein.
2009,
Pubmed
Miwa,
The prototoxin lynx1 acts on nicotinic acetylcholine receptors to balance neuronal activity and survival in vivo.
2006,
Pubmed
Miwa,
lynx1, an endogenous toxin-like modulator of nicotinic acetylcholine receptors in the mammalian CNS.
1999,
Pubmed
,
Xenbase
Montuori,
Multiple activities of a multifaceted receptor: roles of cleaved and soluble uPAR.
2009,
Pubmed
Mordvintsev,
Weak toxin WTX from Naja kaouthia cobra venom interacts with both nicotinic and muscarinic acetylcholine receptors.
2009,
Pubmed
Mordvitsev,
Computer modeling of binding of diverse weak toxins to nicotinic acetylcholine receptors.
2007,
Pubmed
Moriwaki,
Primary sensory neuronal expression of SLURP-1, an endogenous nicotinic acetylcholine receptor ligand.
2009,
Pubmed
Nastopoulos,
Structure of dimeric and monomeric erabutoxin a refined at 1.5 A resolution.
1998,
Pubmed
Nirthanan,
Candoxin, a novel toxin from Bungarus candidus, is a reversible antagonist of muscle (alphabetagammadelta ) but a poorly reversible antagonist of neuronal alpha 7 nicotinic acetylcholine receptors.
2002,
Pubmed
Nirthanan,
Three-finger alpha-neurotoxins and the nicotinic acetylcholine receptor, forty years on.
2004,
Pubmed
Pillet,
Genetic engineering of snake toxins. Role of invariant residues in the structural and functional properties of a curaremimetic toxin, as probed by site-directed mutagenesis.
1993,
Pubmed
Rasch,
Intact and cleaved uPAR forms: diagnostic and prognostic value in cancer.
2008,
Pubmed
Rucktooa,
Insight in nAChR subtype selectivity from AChBP crystal structures.
2009,
Pubmed
Servent,
Muscarinic toxins: tools for the study of the pharmacological and functional properties of muscarinic receptors.
2009,
Pubmed
Song,
Activated cholinergic signaling provides a target in squamous cell lung carcinoma.
2008,
Pubmed
Tekinay,
A role for LYNX2 in anxiety-related behavior.
2009,
Pubmed
Tsetlin,
Snake and snail toxins acting on nicotinic acetylcholine receptors: fundamental aspects and medical applications.
2004,
Pubmed
Tsetlin,
Snake venom alpha-neurotoxins and other 'three-finger' proteins.
1999,
Pubmed
Tsuji,
SLURP-2, a novel member of the human Ly-6 superfamily that is up-regulated in psoriasis vulgaris.
2003,
Pubmed
Utkin,
"Weak toxin" from Naja kaouthia is a nontoxic antagonist of alpha 7 and muscle-type nicotinic acetylcholine receptors.
2001,
Pubmed
,
Xenbase
