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| | <StructureSection load='5v5v' size='340' side='right'caption='[[5v5v]], [[Resolution|resolution]] 4.11Å' scene=''> | | <StructureSection load='5v5v' size='340' side='right'caption='[[5v5v]], [[Resolution|resolution]] 4.11Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5v5v]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V5V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V5V FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5v5v]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V5V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V5V FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5v5w|5v5w]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.11Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nlgn2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), MDGA1, MAMDC3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5v5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v5v OCA], [https://pdbe.org/5v5v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v5v RCSB], [https://www.ebi.ac.uk/pdbsum/5v5v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v5v 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=5v5v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v5v OCA], [http://pdbe.org/5v5v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v5v RCSB], [http://www.ebi.ac.uk/pdbsum/5v5v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v5v ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NLGN2_RAT NLGN2_RAT]] Transmembrane scaffolding protein involved in cell-cell interactions via its interactions with neurexin family members. Mediates cell-cell interactions both in neurons and in other types of cells, such as Langerhans beta cells. Plays a role in synapse function and synaptic signal transmission, especially via gamma-aminobutyric acid receptors (GABA(A) receptors). Functions by recruiting and clustering synaptic proteins. Promotes clustering of postsynaptic GABRG2 and GPHN. Modulates signaling by inhibitory synapses, and thereby plays a role in controlling the ratio of signaling by excitatory and inhibitory synapses and information processing. Required for normal signal amplitude from inhibitory synapses, but is not essential for normal signal frequency. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. Mediates cell-cell interactions between Langerhans beta cells and modulates insulin secretion.<ref>PMID:19755106</ref> <ref>PMID:22528485</ref> [[http://www.uniprot.org/uniprot/MDGA1_HUMAN MDGA1_HUMAN]] Required for radial migration of cortical neurons in the superficial layer of the neocortex (By similarity). Plays a role in the formation or maintenance of inhibitory synapses. May function by inhibiting the activity of NLGN2.<ref>PMID:23248271</ref> | + | [https://www.uniprot.org/uniprot/NLGN2_RAT NLGN2_RAT] Transmembrane scaffolding protein involved in cell-cell interactions via its interactions with neurexin family members. Mediates cell-cell interactions both in neurons and in other types of cells, such as Langerhans beta cells. Plays a role in synapse function and synaptic signal transmission, especially via gamma-aminobutyric acid receptors (GABA(A) receptors). Functions by recruiting and clustering synaptic proteins. Promotes clustering of postsynaptic GABRG2 and GPHN. Modulates signaling by inhibitory synapses, and thereby plays a role in controlling the ratio of signaling by excitatory and inhibitory synapses and information processing. Required for normal signal amplitude from inhibitory synapses, but is not essential for normal signal frequency. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. Mediates cell-cell interactions between Langerhans beta cells and modulates insulin secretion.<ref>PMID:19755106</ref> <ref>PMID:22528485</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: Buffalo rat]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gangwar, S P]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Machius, M]] | + | [[Category: Gangwar SP]] |
| - | [[Category: Rudenko, G]] | + | [[Category: Machius M]] |
| - | [[Category: Cell adhesion]] | + | [[Category: Rudenko G]] |
| - | [[Category: Mdga]]
| + | |
| - | [[Category: Neuroligin]]
| + | |
| - | [[Category: Regulatory complex]]
| + | |
| - | [[Category: Synaptic organizer]]
| + | |
| Structural highlights
Function
NLGN2_RAT Transmembrane scaffolding protein involved in cell-cell interactions via its interactions with neurexin family members. Mediates cell-cell interactions both in neurons and in other types of cells, such as Langerhans beta cells. Plays a role in synapse function and synaptic signal transmission, especially via gamma-aminobutyric acid receptors (GABA(A) receptors). Functions by recruiting and clustering synaptic proteins. Promotes clustering of postsynaptic GABRG2 and GPHN. Modulates signaling by inhibitory synapses, and thereby plays a role in controlling the ratio of signaling by excitatory and inhibitory synapses and information processing. Required for normal signal amplitude from inhibitory synapses, but is not essential for normal signal frequency. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. Mediates cell-cell interactions between Langerhans beta cells and modulates insulin secretion.[1] [2]
Publication Abstract from PubMed
Neuroligins and neurexins promote synapse development and validation by forming trans-synaptic bridges spanning the synaptic cleft. Select pairs promote excitatory and inhibitory synapses, with neuroligin 2 (NLGN2) limited to inhibitory synapses and neuroligin 1 (NLGN1) dominating at excitatory synapses. The cell-surface molecules, MAM domain-containing glycosylphosphatidylinositol anchor 1 (MDGA1) and 2 (MDGA2), regulate trans-synaptic adhesion between neurexins and neuroligins, impacting NLGN2 and NLGN1, respectively. We have determined the molecular mechanism of MDGA action. MDGA1 Ig1-Ig2 is sufficient to bind NLGN2 with nanomolar affinity; its crystal structure reveals an unusual locked rod-shaped array. In the crystal structure of the complex, two MDGA1 Ig1-Ig2 molecules each span the entire NLGN2 dimer. Site-directed mutagenesis confirms the observed interaction interface. Strikingly, Ig1 from MDGA1 binds to the same region on NLGN2 as neurexins do. Thus, MDGAs regulate the formation of neuroligin-neurexin trans-synaptic bridges by sterically blocking access of neurexins to neuroligins.
Molecular Mechanism of MDGA1: Regulation of Neuroligin 2:Neurexin Trans-synaptic Bridges.,Gangwar SP, Zhong X, Seshadrinathan S, Chen H, Machius M, Rudenko G Neuron. 2017 Jun 21;94(6):1132-1141.e4. doi: 10.1016/j.neuron.2017.06.009. PMID:28641112[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Poulopoulos A, Aramuni G, Meyer G, Soykan T, Hoon M, Papadopoulos T, Zhang M, Paarmann I, Fuchs C, Harvey K, Jedlicka P, Schwarzacher SW, Betz H, Harvey RJ, Brose N, Zhang W, Varoqueaux F. Neuroligin 2 drives postsynaptic assembly at perisomatic inhibitory synapses through gephyrin and collybistin. Neuron. 2009 Sep 10;63(5):628-42. doi: 10.1016/j.neuron.2009.08.023. PMID:19755106 doi:http://dx.doi.org/10.1016/j.neuron.2009.08.023
- ↑ Suckow AT, Zhang C, Egodage S, Comoletti D, Taylor P, Miller MT, Sweet IR, Chessler SD. Transcellular neuroligin-2 interactions enhance insulin secretion and are integral to pancreatic beta cell function. J Biol Chem. 2012 Jun 8;287(24):19816-26. doi: 10.1074/jbc.M111.280537. Epub 2012, Apr 23. PMID:22528485 doi:http://dx.doi.org/10.1074/jbc.M111.280537
- ↑ Gangwar SP, Zhong X, Seshadrinathan S, Chen H, Machius M, Rudenko G. Molecular Mechanism of MDGA1: Regulation of Neuroligin 2:Neurexin Trans-synaptic Bridges. Neuron. 2017 Jun 21;94(6):1132-1141.e4. doi: 10.1016/j.neuron.2017.06.009. PMID:28641112 doi:http://dx.doi.org/10.1016/j.neuron.2017.06.009
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