Structural highlights2l03 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. Publication Abstract from PubMedDiscovery of proteins expressed in the central nervous system sharing the three-finger structure with snake alpha-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 muM, ws-LYNX1 competed with (125)I-alpha-bungarotoxin for binding to the acetylcholine-binding proteins (AChBPs) and to Torpedo nAChR. Exposure of Xenopus oocytes expressing alpha7 nAChRs to 1 muM ws-LYNX1 enhanced the response to acetylcholine, but no effect was detected on alpha4beta2 and alpha3beta2 nAChRs. Increasing ws-LYNX1 concentration to 10 muM 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. 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 J Biol Chem. 2011 Mar 25;286(12):10618-27. Epub 2011 Jan 20. PMID:21252236[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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