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| | ==Crystal structure of the chicken MDGA1 ectodomain in complex with the human neuroligin 1 (NL1(-A-B)) cholinesterase domain.== | | ==Crystal structure of the chicken MDGA1 ectodomain in complex with the human neuroligin 1 (NL1(-A-B)) cholinesterase domain.== |
| - | <StructureSection load='5oj6' size='340' side='right' caption='[[5oj6]], [[Resolution|resolution]] 3.30Å' scene=''> | + | <StructureSection load='5oj6' size='340' side='right'caption='[[5oj6]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5oj6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Chick Chick] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OJ6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5OJ6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5oj6]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5OJ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5OJ6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <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]] 3.3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NLGN1, KIAA1070 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), MDGA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5oj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oj6 OCA], [http://pdbe.org/5oj6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5oj6 RCSB], [http://www.ebi.ac.uk/pdbsum/5oj6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5oj6 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=5oj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5oj6 OCA], [https://pdbe.org/5oj6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5oj6 RCSB], [https://www.ebi.ac.uk/pdbsum/5oj6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5oj6 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NLGN1_HUMAN NLGN1_HUMAN]] Cell surface protein involved in cell-cell-interactions via its interactions with neurexin family members. Plays a role in synapse function and synaptic signal transmission, and probably mediates its effects by recruiting and clustering other synaptic proteins. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. May be involved in specification of excitatory synapses. Required to maintain wakefulness quality and normal synchrony of cerebral cortex activity during wakefulness and sleep.[UniProtKB:Q99K10] | + | [https://www.uniprot.org/uniprot/NLGN1_HUMAN NLGN1_HUMAN] Cell surface protein involved in cell-cell-interactions via its interactions with neurexin family members. Plays a role in synapse function and synaptic signal transmission, and probably mediates its effects by recruiting and clustering other synaptic proteins. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. May be involved in specification of excitatory synapses. Required to maintain wakefulness quality and normal synchrony of cerebral cortex activity during wakefulness and sleep.[UniProtKB:Q99K10] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5oj6" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5oj6" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Neuroligin|Neuroligin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Chick]] | + | [[Category: Gallus gallus]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Aricescu, A R]] | + | [[Category: Large Structures]] |
| - | [[Category: Clayton, A J]] | + | [[Category: Aricescu AR]] |
| - | [[Category: Elegheert, J]] | + | [[Category: Clayton AJ]] |
| - | [[Category: Cell adhesion]] | + | [[Category: Elegheert J]] |
| - | [[Category: Neuroligin-neurexin]]
| + | |
| - | [[Category: Synapse formation]]
| + | |
| - | [[Category: Synaptic transmission]]
| + | |
| Structural highlights
Function
NLGN1_HUMAN Cell surface protein involved in cell-cell-interactions via its interactions with neurexin family members. Plays a role in synapse function and synaptic signal transmission, and probably mediates its effects by recruiting and clustering other synaptic proteins. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. May be involved in specification of excitatory synapses. Required to maintain wakefulness quality and normal synchrony of cerebral cortex activity during wakefulness and sleep.[UniProtKB:Q99K10]
Publication Abstract from PubMed
Neuroligin-neurexin (NL-NRX) complexes are fundamental synaptic organizers in the central nervous system. An accurate spatial and temporal control of NL-NRX signaling is crucial to balance excitatory and inhibitory neurotransmission, and perturbations are linked with neurodevelopmental and psychiatric disorders. MDGA proteins bind NLs and control their function and interaction with NRXs via unknown mechanisms. Here, we report crystal structures of MDGA1, the NL1-MDGA1 complex, and a spliced NL1 isoform. Two large, multi-domain MDGA molecules fold into rigid triangular structures, cradling a dimeric NL to prevent NRX binding. Structural analyses guided the discovery of a broad, splicing-modulated interaction network between MDGA and NL family members and helped rationalize the impact of autism-linked mutations. We demonstrate that expression levels largely determine whether MDGAs act selectively or suppress the synapse organizing function of multiple NLs. These results illustrate a potentially brain-wide regulatory mechanism for NL-NRX signaling modulation.
Structural Mechanism for Modulation of Synaptic Neuroligin-Neurexin Signaling by MDGA Proteins.,Elegheert J, Cvetkovska V, Clayton AJ, Heroven C, Vennekens KM, Smukowski SN, Regan MC, Jia W, Smith AC, Furukawa H, Savas JN, de Wit J, Begbie J, Craig AM, Aricescu AR Neuron. 2017 Aug 16;95(4):896-913.e10. doi: 10.1016/j.neuron.2017.07.040. PMID:28817804[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Elegheert J, Cvetkovska V, Clayton AJ, Heroven C, Vennekens KM, Smukowski SN, Regan MC, Jia W, Smith AC, Furukawa H, Savas JN, de Wit J, Begbie J, Craig AM, Aricescu AR. Structural Mechanism for Modulation of Synaptic Neuroligin-Neurexin Signaling by MDGA Proteins. Neuron. 2017 Aug 16;95(4):896-913.e10. doi: 10.1016/j.neuron.2017.07.040. PMID:28817804 doi:http://dx.doi.org/10.1016/j.neuron.2017.07.040
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