2n99: Difference between revisions

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==Solution structure of the SLURP-2, a secreted isoform of Lynx1==
==Solution structure of the SLURP-2, a secreted isoform of Lynx1==
<StructureSection load='2n99' size='340' side='right'caption='[[2n99]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
<StructureSection load='2n99' size='340' side='right'caption='[[2n99]]' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2n99]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N99 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N99 FirstGlance]. <br>
<table><tr><td colspan='2'>[[2n99]] 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=2N99 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N99 FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">LYNX1, SLURP2 ([https://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=2n99 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n99 OCA], [https://pdbe.org/2n99 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n99 RCSB], [https://www.ebi.ac.uk/pdbsum/2n99 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n99 ProSAT]</span></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=2n99 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n99 OCA], [https://pdbe.org/2n99 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n99 RCSB], [https://www.ebi.ac.uk/pdbsum/2n99 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n99 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[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>
[https://www.uniprot.org/uniprot/SLUR2_HUMAN SLUR2_HUMAN] Binds and may modulate the functional properties of nicotinic and muscarinic acetylcholine receptors. May regulate keratinocytes proliferation, differentiation and apoptosis. In vitro moderately inhibits ACh-evoked currents of alpha-3:beta-2-containing nAChRs and strongly these of alpha-4:beta-2-containing nAChRs, modulates alpha-7-containing nAChRs, and inhibits nicotine-induced signaling probably implicating alpha-3:beta-4-containing nAChRs. Proposed to act on alpha-3:beta-2 and alpha-7 nAChRs in an orthosteric, and on mAChRs, such as CHRM1 and CHRM3, in an allosteric manner.<ref>PMID:16575903</ref> <ref>PMID:27485575</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: Large Structures]]
[[Category: Large Structures]]
[[Category: Arseniev, A S]]
[[Category: Arseniev AS]]
[[Category: Lyukmanova, E N]]
[[Category: Lyukmanova EN]]
[[Category: Paramonov, A S]]
[[Category: Paramonov AS]]
[[Category: Shenkarev, Z O]]
[[Category: Shenkarev ZO]]
[[Category: Cell proliferation]]
[[Category: Epithelium]]
[[Category: Keratinocyte]]
[[Category: Muscarinic acetylcholine receptor]]
[[Category: Neuromodulator]]
[[Category: Neuropeptide]]
[[Category: Nicotinic acetylcholine receptor]]
[[Category: Three-finger protein]]

Revision as of 13:24, 15 March 2023

Solution structure of the SLURP-2, a secreted isoform of Lynx1Solution structure of the SLURP-2, a secreted isoform of Lynx1

Structural highlights

2n99 is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SLUR2_HUMAN Binds and may modulate the functional properties of nicotinic and muscarinic acetylcholine receptors. May regulate keratinocytes proliferation, differentiation and apoptosis. In vitro moderately inhibits ACh-evoked currents of alpha-3:beta-2-containing nAChRs and strongly these of alpha-4:beta-2-containing nAChRs, modulates alpha-7-containing nAChRs, and inhibits nicotine-induced signaling probably implicating alpha-3:beta-4-containing nAChRs. Proposed to act on alpha-3:beta-2 and alpha-7 nAChRs in an orthosteric, and on mAChRs, such as CHRM1 and CHRM3, in an allosteric manner.[1] [2]

Publication Abstract from PubMed

Human-secreted Ly-6/uPAR-related protein-2 (SLURP-2) regulates the growth and differentiation of epithelial cells. Previously, the auto/paracrine activity of SLURP-2 was considered to be mediated via its interaction with the alpha3beta2 subtype of the nicotinic acetylcholine receptors (nAChRs). Here, we describe the structure and pharmacology of a recombinant analogue of SLURP-2. Nuclear magnetic resonance spectroscopy revealed a 'three-finger' fold of SLURP-2 with a conserved beta-structural core and three protruding loops. Affinity purification using cortical extracts revealed that SLURP-2 could interact with the alpha3, alpha4, alpha5, alpha7, beta2, and beta4 nAChR subunits, revealing its broader pharmacological profile. SLURP-2 inhibits acetylcholine-evoked currents at alpha4beta2 and alpha3beta2-nAChRs (IC50 ~0.17 and >3 muM, respectively) expressed in Xenopus oocytes. In contrast, at alpha7-nAChRs, SLURP-2 significantly enhances acetylcholine-evoked currents at concentrations <1 muM but induces inhibition at higher concentrations. SLURP-2 allosterically interacts with human M1 and M3 muscarinic acetylcholine receptors (mAChRs) that are overexpressed in CHO cells. SLURP-2 was found to promote the proliferation of human oral keratinocytes via interactions with alpha3beta2-nAChRs, while it inhibited cell growth via alpha7-nAChRs. SLURP-2/mAChRs interactions are also probably involved in the control of keratinocyte growth. Computer modeling revealed possible SLURP-2 binding to the 'classical' orthosteric agonist/antagonist binding sites at alpha7 and alpha3beta2-nAChRs.

Secreted Isoform of Human Lynx1 (SLURP-2): Spatial Structure and Pharmacology of Interactions with Different Types of Acetylcholine Receptors.,Lyukmanova EN, Shulepko MA, Shenkarev ZO, Bychkov ML, Paramonov AS, Chugunov AO, Kulbatskii DS, Arvaniti M, Dolejsi E, Schaer T, Arseniev AS, Efremov RG, Thomsen MS, Dolezal V, Bertrand D, Dolgikh DA, Kirpichnikov MP Sci Rep. 2016 Aug 3;6:30698. doi: 10.1038/srep30698. PMID:27485575[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ 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
  2. ↑ Lyukmanova EN, Shulepko MA, Shenkarev ZO, Bychkov ML, Paramonov AS, Chugunov AO, Kulbatskii DS, Arvaniti M, Dolejsi E, Schaer T, Arseniev AS, Efremov RG, Thomsen MS, Dolezal V, Bertrand D, Dolgikh DA, Kirpichnikov MP. Secreted Isoform of Human Lynx1 (SLURP-2): Spatial Structure and Pharmacology of Interactions with Different Types of Acetylcholine Receptors. Sci Rep. 2016 Aug 3;6:30698. doi: 10.1038/srep30698. PMID:27485575 doi:http://dx.doi.org/10.1038/srep30698
  3. ↑ Lyukmanova EN, Shulepko MA, Shenkarev ZO, Bychkov ML, Paramonov AS, Chugunov AO, Kulbatskii DS, Arvaniti M, Dolejsi E, Schaer T, Arseniev AS, Efremov RG, Thomsen MS, Dolezal V, Bertrand D, Dolgikh DA, Kirpichnikov MP. Secreted Isoform of Human Lynx1 (SLURP-2): Spatial Structure and Pharmacology of Interactions with Different Types of Acetylcholine Receptors. Sci Rep. 2016 Aug 3;6:30698. doi: 10.1038/srep30698. PMID:27485575 doi:http://dx.doi.org/10.1038/srep30698
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