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| | ==Structural characterization of a synaptic adhesion complex== | | ==Structural characterization of a synaptic adhesion complex== |
| - | <StructureSection load='4yeb' size='340' side='right' caption='[[4yeb]], [[Resolution|resolution]] 3.19Å' scene=''> | + | <StructureSection load='4yeb' size='340' side='right'caption='[[4yeb]], [[Resolution|resolution]] 3.19Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4yeb]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YEB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YEB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4yeb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YEB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YEB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4rmk|4rmk]], [[4rml|4rml]]</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=4yeb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yeb OCA], [https://pdbe.org/4yeb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yeb RCSB], [https://www.ebi.ac.uk/pdbsum/4yeb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yeb ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Lphn3, Kiaa0768, Lec3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Flrt3, mCG_130708 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4yeb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yeb OCA], [http://pdbe.org/4yeb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yeb RCSB], [http://www.ebi.ac.uk/pdbsum/4yeb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yeb ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/LPHN3_MOUSE LPHN3_MOUSE]] May be involved in the development of glutamatergic synapses in the cortex. Important in determining the connectivity rates between the principal neurons in the cortex.<ref>PMID:24739570</ref> | + | [https://www.uniprot.org/uniprot/AGRL3_MOUSE AGRL3_MOUSE] Plays a role in cell-cell adhesion and neuron guidance via its interactions with FLRT2 and FLRT3 that are expressed at the surface of adjacent cells (PubMed:22405201, PubMed:25728924, PubMed:26235031). Plays a role in the development of glutamatergic synapses in the cortex (PubMed:22405201, PubMed:24739570). Important in determining the connectivity rates between the principal neurons in the cortex (PubMed:24739570).<ref>PMID:22405201</ref> <ref>PMID:24739570</ref> <ref>PMID:25728924</ref> <ref>PMID:26235031</ref> |
| | <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 4yeb" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4yeb" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Latrophilin|Latrophilin]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Bergami, F]] | + | [[Category: Mus musculus]] |
| - | [[Category: Comoletti, D]] | + | [[Category: Bergami F]] |
| - | [[Category: Daake, S von]] | + | [[Category: Comoletti D]] |
| - | [[Category: Demeler, B]] | + | [[Category: Demeler B]] |
| - | [[Category: Hendrickson, W A]] | + | [[Category: Hendrickson WA]] |
| - | [[Category: Lee, D]] | + | [[Category: Lee D]] |
| - | [[Category: Li, S]] | + | [[Category: Li S]] |
| - | [[Category: Liu, Q]] | + | [[Category: Liu Q]] |
| - | [[Category: Martini, F]] | + | [[Category: Martini F]] |
| - | [[Category: Ranaivoson, F M]] | + | [[Category: Ranaivoson FM]] |
| - | [[Category: Central nervous system]] | + | [[Category: Von Daake S]] |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Flrt3]]
| + | |
| - | [[Category: Latrophilin 3]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
AGRL3_MOUSE Plays a role in cell-cell adhesion and neuron guidance via its interactions with FLRT2 and FLRT3 that are expressed at the surface of adjacent cells (PubMed:22405201, PubMed:25728924, PubMed:26235031). Plays a role in the development of glutamatergic synapses in the cortex (PubMed:22405201, PubMed:24739570). Important in determining the connectivity rates between the principal neurons in the cortex (PubMed:24739570).[1] [2] [3] [4]
Publication Abstract from PubMed
Latrophilins (LPHNs) are adhesion-like G-protein-coupled receptors implicated in attention-deficit/hyperactivity disorder. Recently, LPHN3 was found to regulate excitatory synapse number through trans interactions with fibronectin leucine-rich repeat transmembrane 3 (FLRT3). By isothermal titration calorimetry, we determined that only the olfactomedin (OLF) domain of LPHN3 is necessary for FLRT3 association. By multi-crystal native single-wavelength anomalous diffraction phasing, we determined the crystal structure of the OLF domain. This structure is a five-bladed beta propeller with a Ca2+ ion bound in the central pore, which is capped by a mobile loop that allows the ion to exchange with the solvent. The crystal structure of the OLF/FLRT3 complex shows that LPHN3-OLF in the closed state binds with high affinity to the concave face of FLRT3-LRR with a combination of hydrophobic and charged residues. Our study provides structural and functional insights into the molecular mechanism underlying the contribution of LPHN3/FLRT3 to the development of glutamatergic synapses.
Structural and Mechanistic Insights into the Latrophilin3-FLRT3 Complex that Mediates Glutamatergic Synapse Development.,Ranaivoson FM, Liu Q, Martini F, Bergami F, von Daake S, Li S, Lee D, Demeler B, Hendrickson WA, Comoletti D Structure. 2015 Jul 28. pii: S0969-2126(15)00275-0. doi:, 10.1016/j.str.2015.06.022. PMID:26235031[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ O'Sullivan ML, de Wit J, Savas JN, Comoletti D, Otto-Hitt S, Yates JR 3rd, Ghosh A. FLRT proteins are endogenous latrophilin ligands and regulate excitatory synapse development. Neuron. 2012 Mar 8;73(5):903-10. doi: 10.1016/j.neuron.2012.01.018. PMID:22405201 doi:http://dx.doi.org/10.1016/j.neuron.2012.01.018
- ↑ O'Sullivan ML, Martini F, von Daake S, Comoletti D, Ghosh A. LPHN3, a presynaptic adhesion-GPCR implicated in ADHD, regulates the strength of neocortical layer 2/3 synaptic input to layer 5. Neural Dev. 2014 Apr 17;9:7. doi: 10.1186/1749-8104-9-7. PMID:24739570 doi:http://dx.doi.org/10.1186/1749-8104-9-7
- ↑ Jackson VA, Del Toro D, Carrasquero M, Roversi P, Harlos K, Klein R, Seiradake E. Structural Basis of Latrophilin-FLRT Interaction. Structure. 2015 Feb 17. pii: S0969-2126(15)00037-4. doi:, 10.1016/j.str.2015.01.013. PMID:25728924 doi:http://dx.doi.org/10.1016/j.str.2015.01.013
- ↑ Ranaivoson FM, Liu Q, Martini F, Bergami F, von Daake S, Li S, Lee D, Demeler B, Hendrickson WA, Comoletti D. Structural and Mechanistic Insights into the Latrophilin3-FLRT3 Complex that Mediates Glutamatergic Synapse Development. Structure. 2015 Jul 28. pii: S0969-2126(15)00275-0. doi:, 10.1016/j.str.2015.06.022. PMID:26235031 doi:http://dx.doi.org/10.1016/j.str.2015.06.022
- ↑ Ranaivoson FM, Liu Q, Martini F, Bergami F, von Daake S, Li S, Lee D, Demeler B, Hendrickson WA, Comoletti D. Structural and Mechanistic Insights into the Latrophilin3-FLRT3 Complex that Mediates Glutamatergic Synapse Development. Structure. 2015 Jul 28. pii: S0969-2126(15)00275-0. doi:, 10.1016/j.str.2015.06.022. PMID:26235031 doi:http://dx.doi.org/10.1016/j.str.2015.06.022
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