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| | ==Crystal Structure of human MDGA1 and human neuroligin-2 complex== | | ==Crystal Structure of human MDGA1 and human neuroligin-2 complex== |
| - | <StructureSection load='5xeq' size='340' side='right' caption='[[5xeq]], [[Resolution|resolution]] 3.14Å' scene=''> | + | <StructureSection load='5xeq' size='340' side='right'caption='[[5xeq]], [[Resolution|resolution]] 3.14Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5xeq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XEQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5XEQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5xeq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5XEQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5XEQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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]] 3.136Å</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=5xeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xeq OCA], [http://pdbe.org/5xeq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5xeq RCSB], [http://www.ebi.ac.uk/pdbsum/5xeq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5xeq ProSAT]</span></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=5xeq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5xeq OCA], [https://pdbe.org/5xeq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5xeq RCSB], [https://www.ebi.ac.uk/pdbsum/5xeq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5xeq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NLGN2_HUMAN NLGN2_HUMAN]] 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 (By similarity). [[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/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> |
| | <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: Kim, D]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Kim, H M]] | + | [[Category: Large Structures]] |
| - | [[Category: Kim, J A]] | + | [[Category: Kim D]] |
| - | [[Category: Cell adhesion]] | + | [[Category: Kim HM]] |
| - | [[Category: Immunogloubulin-like domain]] | + | [[Category: Kim JA]] |
| Structural highlights
Function
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.[1]
Publication Abstract from PubMed
Membrane-associated mucin domain-containing glycosylphosphatidylinositol anchor proteins (MDGAs) bind directly to neuroligin-1 (NL1) and neuroligin-2 (NL2), thereby respectively regulating excitatory and inhibitory synapse development. However, the mechanisms by which MDGAs modulate NL activity to specify development of the two synapse types remain unclear. Here, we determined the crystal structures of human NL2/MDGA1 Ig1-3 complex, revealing their stable 2:2 arrangement with three interaction interfaces. Cell-based assays using structure-guided, site-directed MDGA1 mutants showed that all three contact patches were required for the MDGA's negative regulation of NL2-mediated synaptogenic activity. Furthermore, MDGA1 competed with neurexins for NL2 via its Ig1 domain. The binding affinities of both MDGA1 and MDGA2 for NL1 and NL2 were similar, consistent with the structural prediction of similar binding interfaces. However, MDGA1 selectively associated with NL2, but not NL1, in vivo. These findings collectively provide structural insights into the mechanism by which MDGAs negatively modulate synapse development governed by NLs/neurexins.
Structural Insights into Modulation of Neurexin-Neuroligin Trans-synaptic Adhesion by MDGA1/Neuroligin-2 Complex.,Kim JA, Kim D, Won SY, Han KA, Park D, Cho E, Yun N, An HJ, Um JW, Kim E, Lee JO, Ko J, Kim HM Neuron. 2017 Jun 21;94(6):1121-1131.e6. doi: 10.1016/j.neuron.2017.05.034. PMID:28641111[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lee K, Kim Y, Lee SJ, Qiang Y, Lee D, Lee HW, Kim H, Je HS, Sudhof TC, Ko J. MDGAs interact selectively with neuroligin-2 but not other neuroligins to regulate inhibitory synapse development. Proc Natl Acad Sci U S A. 2013 Jan 2;110(1):336-41. doi: 10.1073/pnas.1219987110., Epub 2012 Dec 17. PMID:23248271 doi:http://dx.doi.org/10.1073/pnas.1219987110
- ↑ Kim JA, Kim D, Won SY, Han KA, Park D, Cho E, Yun N, An HJ, Um JW, Kim E, Lee JO, Ko J, Kim HM. Structural Insights into Modulation of Neurexin-Neuroligin Trans-synaptic Adhesion by MDGA1/Neuroligin-2 Complex. Neuron. 2017 Jun 21;94(6):1121-1131.e6. doi: 10.1016/j.neuron.2017.05.034. PMID:28641111 doi:http://dx.doi.org/10.1016/j.neuron.2017.05.034
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