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| | ==Spatial structure of water-soluble Lynx1== | | ==Spatial structure of water-soluble Lynx1== |
| - | <StructureSection load='2l03' size='340' side='right' caption='[[2l03]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2l03' size='340' side='right'caption='[[2l03]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2l03]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L03 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2L03 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2l03]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L03 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L03 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LYNX1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2l03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l03 OCA], [https://pdbe.org/2l03 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l03 RCSB], [https://www.ebi.ac.uk/pdbsum/2l03 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l03 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2l03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l03 OCA], [http://pdbe.org/2l03 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2l03 RCSB], [http://www.ebi.ac.uk/pdbsum/2l03 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2l03 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LYNX1_HUMAN LYNX1_HUMAN]] Acts in different tissues through interaction to nicotinic acetylcholine receptors (nAChRs). In brain, isoform 2 modulates functional properties of nAChRs to prevent excessive excitation, and hence neurodegeneration. Enhances desensitization by increasing both the rate and extent of desensitization of alpha(4)beta(2) nAChRs and slowing recovery from desensitization. Promotes large amplitude ACh-evoked currents through alpha(4)beta(2) nAChRs (By similarity). Prevents plasticity in the primary visual cortex late in life (By similarity). In keratinocytes, isoform 3 delays differentiation and prevents apoptosis.<ref>PMID:16575903</ref> | + | [https://www.uniprot.org/uniprot/LYNX1_HUMAN LYNX1_HUMAN] Acts in different tissues through interaction to nicotinic acetylcholine receptors (nAChRs). In brain, isoform 2 modulates functional properties of nAChRs to prevent excessive excitation, and hence neurodegeneration. Enhances desensitization by increasing both the rate and extent of desensitization of alpha(4)beta(2) nAChRs and slowing recovery from desensitization. Promotes large amplitude ACh-evoked currents through alpha(4)beta(2) nAChRs (By similarity). Prevents plasticity in the primary visual cortex late in life (By similarity). In keratinocytes, isoform 3 delays differentiation and prevents apoptosis.<ref>PMID:16575903</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Arseniev, A S]] | + | [[Category: Large Structures]] |
| - | [[Category: Mineev, K S]] | + | [[Category: Arseniev AS]] |
| - | [[Category: Shenkarev, Z O]] | + | [[Category: Mineev KS]] |
| - | [[Category: Acetylcholine receptor]] | + | [[Category: Shenkarev ZO]] |
| - | [[Category: Endogenic neuromodulator]]
| + | |
| - | [[Category: Lynx1]]
| + | |
| - | [[Category: Neuropeptide]]
| + | |
| - | [[Category: Three-finger toxin]]
| + | |
| Structural highlights
Function
LYNX1_HUMAN Acts in different tissues through interaction to nicotinic acetylcholine receptors (nAChRs). In brain, isoform 2 modulates functional properties of nAChRs to prevent excessive excitation, and hence neurodegeneration. Enhances desensitization by increasing both the rate and extent of desensitization of alpha(4)beta(2) nAChRs and slowing recovery from desensitization. Promotes large amplitude ACh-evoked currents through alpha(4)beta(2) nAChRs (By similarity). Prevents plasticity in the primary visual cortex late in life (By similarity). In keratinocytes, isoform 3 delays differentiation and prevents apoptosis.[1]
Publication Abstract from PubMed
Discovery 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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Arredondo J, Chernyavsky AI, Jolkovsky DL, Webber RJ, Grando SA. SLURP-2: A novel cholinergic signaling peptide in human mucocutaneous epithelium. J Cell Physiol. 2006 Jul;208(1):238-45. PMID:16575903 doi:http://dx.doi.org/10.1002/jcp.20661
- ↑ 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. NMR structure and action on nicotinic acetylcholine receptors of water-soluble domain of human LYNX1. J Biol Chem. 2011 Mar 25;286(12):10618-27. Epub 2011 Jan 20. PMID:21252236 doi:10.1074/jbc.M110.189100
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