2wv3: Difference between revisions
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< | ==Neuroplastin-55 binds to and signals through the fibroblast growth factor receptor== | ||
<StructureSection load='2wv3' size='340' side='right'caption='[[2wv3]], [[Resolution|resolution]] 1.95Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2wv3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WV3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WV3 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=2wv3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wv3 OCA], [https://pdbe.org/2wv3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wv3 RCSB], [https://www.ebi.ac.uk/pdbsum/2wv3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wv3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/NPTN_RAT NPTN_RAT] Probable homophilic and heterophilic cell adhesion molecule involved in long term potentiation at hippocampal excitatory synapses through activation of p38MAPK. May also regulate neurite outgrowth by activating the FGFR1 signaling pathway. May play a role in synaptic plasticity.<ref>PMID:10759566</ref> <ref>PMID:16925595</ref> <ref>PMID:19952283</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wv/2wv3_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2wv3 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Neuroplastin (Np) is a glycoprotein belonging to the immunoglobulin superfamily of cell adhesion molecules (CAMs) and existing in two isoforms, Np55 and Np65, named according to their molecular weights. The extracellular part of Np65 contains three immunoglobulin (Ig)-like modules (Ig1, Ig2, and Ig3), whereas Np55 lacks the Ig1 module. Of these two isoforms, only Np65 is involved in homophilic interactions resulting in cell adhesion, whereas the role of Np55 is poorly understood. The present study reports for the first time the crystal structure of the ectodomain of Np55 at 1.95-A resolution and demonstrates that Np55 binds to and activates the fibroblast growth factor receptor 1 (FGFR1). Furthermore, we identify a sequence motif in the Ig2 module of Np55 interacting with FGFR1 and show that a synthetic peptide encompassing this motif, termed narpin, binds to and activates FGFR1. We show that both Np55 and the narpin peptide induce neurite outgrowth through FGFR1 activation and that Np55 increases synaptic calcium concentration in an FGFR1-dependent manner. Moreover, we demonstrate that narpin has an antidepressive-like effect in rats subjected to the forced swim test, suggesting that Np55-induced signaling may be involved in synaptic plasticity in vivo. Owczarek, S., Kiryushko, D., Larsen, M. H., Kastrup, J. S., Gajhede, M., Sandi, C., Berezin, V., Bock, E., Soroka, V. Neuroplastin-55 binds to and signals through the fibroblast growth factor receptor. | |||
Neuroplastin-55 binds to and signals through the fibroblast growth factor receptor.,Owczarek S, Kiryushko D, Larsen MH, Kastrup JS, Gajhede M, Sandi C, Berezin V, Bock E, Soroka V FASEB J. 2010 Apr;24(4):1139-50. Epub 2009 Dec 1. PMID:19952283<ref>PMID:19952283</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2wv3" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
== | |||
< | |||
[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Berezin | [[Category: Berezin V]] | ||
[[Category: Bock | [[Category: Bock E]] | ||
[[Category: Gajhede | [[Category: Gajhede M]] | ||
[[Category: Kastrup | [[Category: Kastrup JS]] | ||
[[Category: Owczarek | [[Category: Owczarek S]] | ||
[[Category: Soroka | [[Category: Soroka V]] | ||
Latest revision as of 11:03, 23 October 2024
Neuroplastin-55 binds to and signals through the fibroblast growth factor receptorNeuroplastin-55 binds to and signals through the fibroblast growth factor receptor
Structural highlights
FunctionNPTN_RAT Probable homophilic and heterophilic cell adhesion molecule involved in long term potentiation at hippocampal excitatory synapses through activation of p38MAPK. May also regulate neurite outgrowth by activating the FGFR1 signaling pathway. May play a role in synaptic plasticity.[1] [2] [3] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedNeuroplastin (Np) is a glycoprotein belonging to the immunoglobulin superfamily of cell adhesion molecules (CAMs) and existing in two isoforms, Np55 and Np65, named according to their molecular weights. The extracellular part of Np65 contains three immunoglobulin (Ig)-like modules (Ig1, Ig2, and Ig3), whereas Np55 lacks the Ig1 module. Of these two isoforms, only Np65 is involved in homophilic interactions resulting in cell adhesion, whereas the role of Np55 is poorly understood. The present study reports for the first time the crystal structure of the ectodomain of Np55 at 1.95-A resolution and demonstrates that Np55 binds to and activates the fibroblast growth factor receptor 1 (FGFR1). Furthermore, we identify a sequence motif in the Ig2 module of Np55 interacting with FGFR1 and show that a synthetic peptide encompassing this motif, termed narpin, binds to and activates FGFR1. We show that both Np55 and the narpin peptide induce neurite outgrowth through FGFR1 activation and that Np55 increases synaptic calcium concentration in an FGFR1-dependent manner. Moreover, we demonstrate that narpin has an antidepressive-like effect in rats subjected to the forced swim test, suggesting that Np55-induced signaling may be involved in synaptic plasticity in vivo. Owczarek, S., Kiryushko, D., Larsen, M. H., Kastrup, J. S., Gajhede, M., Sandi, C., Berezin, V., Bock, E., Soroka, V. Neuroplastin-55 binds to and signals through the fibroblast growth factor receptor. Neuroplastin-55 binds to and signals through the fibroblast growth factor receptor.,Owczarek S, Kiryushko D, Larsen MH, Kastrup JS, Gajhede M, Sandi C, Berezin V, Bock E, Soroka V FASEB J. 2010 Apr;24(4):1139-50. Epub 2009 Dec 1. PMID:19952283[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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