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| | ==Octameric complex of Latrophilin 3 (Lec, Olf) , Unc5D (Ig, Ig2, TSP1) and FLRT2 (LRR)== | | ==Octameric complex of Latrophilin 3 (Lec, Olf) , Unc5D (Ig, Ig2, TSP1) and FLRT2 (LRR)== |
| - | <StructureSection load='5ftt' size='340' side='right' caption='[[5ftt]], [[Resolution|resolution]] 3.40Å' scene=''> | + | <StructureSection load='5ftt' size='340' side='right'caption='[[5ftt]], [[Resolution|resolution]] 3.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ftt]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FTT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FTT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ftt]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] 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=5FTT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FTT 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=NA:SODIUM+ION'>NA</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]] 3.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ftu|5ftu]]</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=NA:SODIUM+ION'>NA</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=5ftt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ftt OCA], [http://pdbe.org/5ftt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ftt RCSB], [http://www.ebi.ac.uk/pdbsum/5ftt PDBsum]</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=5ftt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ftt OCA], [https://pdbe.org/5ftt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ftt RCSB], [https://www.ebi.ac.uk/pdbsum/5ftt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ftt ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UNC5D_RAT UNC5D_RAT]] Receptor for the netrin NTN4 that promotes neuronal cell survival. Plays a role in cell-cell adhesion and cell guidance. Receptor for netrin involved in cell migration. Plays a role in axon guidance by mediating axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. May play a role in apoptosis in response to DNA damage. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (By similarity). Mediates cell-cell adhesion via its interaction with FLRT3 on an adjacent cell (By similarity).[UniProtKB:Q6UXZ4][UniProtKB:Q8K1S2] [[http://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> [[http://www.uniprot.org/uniprot/FLRT2_MOUSE FLRT2_MOUSE]] Functions in cell-cell adhesion, cell migration and axon guidance. Mediates cell-cell adhesion via its interactions with ADGRL3 and probably also other latrophilins that are expressed at the surface of adjacent cells (PubMed:21350012, PubMed:25728924 PubMed:25374360). May play a role in the migration of cortical neurons during brain development via its interaction with UNC5D (PubMed:21673655). Mediates axon growth cone collapse and plays a repulsive role in neuron guidance via its interaction with UNC5D, and possibly also other UNC-5 family members (PubMed:21673655, PubMed:25728924). Plays a role in fibroblast growth factor-mediated signaling cascades (PubMed:16872596). Required for normal organization of the cardiac basement membrane during embryogenesis, and for normal embryonic epicardium and heart morphogenesis (PubMed:21350012).<ref>PMID:16872596</ref> <ref>PMID:21350012</ref> <ref>PMID:21673655</ref> <ref>PMID:25374360</ref> <ref>PMID:25728924</ref> | + | [https://www.uniprot.org/uniprot/UNC5D_RAT UNC5D_RAT] Receptor for the netrin NTN4 that promotes neuronal cell survival. Plays a role in cell-cell adhesion and cell guidance. Receptor for netrin involved in cell migration. Plays a role in axon guidance by mediating axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. May play a role in apoptosis in response to DNA damage. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (By similarity). Mediates cell-cell adhesion via its interaction with FLRT3 on an adjacent cell (By similarity).[UniProtKB:Q6UXZ4][UniProtKB:Q8K1S2] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| | + | *[[Latrophilin|Latrophilin]] |
| | *[[Netrin receptor|Netrin receptor]] | | *[[Netrin receptor|Netrin receptor]] |
| | == References == | | == References == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Carrasquero, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Chavent, M]] | + | [[Category: Mus musculus]] |
| - | [[Category: Comoletti, D]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Jackson, V A]] | + | [[Category: Carrasquero M]] |
| - | [[Category: Klein, R]]
| + | [[Category: Chavent M]] |
| - | [[Category: Mehmood, S]]
| + | [[Category: Comoletti D]] |
| - | [[Category: Ranaivoson, F M]]
| + | [[Category: Jackson VA]] |
| - | [[Category: Robinson, C V]] | + | [[Category: Klein R]] |
| - | [[Category: Roversi, P]]
| + | [[Category: Mehmood S]] |
| - | [[Category: Sansom, M S.P]]
| + | [[Category: Ranaivoson FM]] |
| - | [[Category: Seiradake, E]] | + | [[Category: Robinson CV]] |
| - | [[Category: Seyit-Bremer, G]]
| + | [[Category: Roversi P]] |
| - | [[Category: Toro, D del]]
| + | [[Category: Sansom MSP]] |
| - | [[Category: Adgr]] | + | [[Category: Seiradake E]] |
| - | [[Category: Adgrl]] | + | [[Category: Seyit-Bremer G]] |
| - | [[Category: Adgrl3]] | + | [[Category: Del Toro D]] |
| - | [[Category: Adhesion]] | + | |
| - | [[Category: Beta propeller]] | + | |
| - | [[Category: Flrt]] | + | |
| - | [[Category: Flrt2]] | + | |
| - | [[Category: Gpcr]] | + | |
| - | [[Category: Guidance]] | + | |
| - | [[Category: Immunoglobulin]]
| + | |
| - | [[Category: Latrophilin]]
| + | |
| - | [[Category: Lectin]]
| + | |
| - | [[Category: Leucine-rich repeat]]
| + | |
| - | [[Category: Lphn]] | + | |
| - | [[Category: Lphn3]]
| + | |
| - | [[Category: Lrr]]
| + | |
| - | [[Category: Netrin receptor]]
| + | |
| - | [[Category: Octamer]]
| + | |
| - | [[Category: Olfactomedin]]
| + | |
| - | [[Category: Repulsion]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| - | [[Category: Signalling protein]]
| + | |
| - | [[Category: Thrombospondin]]
| + | |
| - | [[Category: Unc5]]
| + | |
| - | [[Category: Unc5d]]
| + | |
| - | [[Category: Uncoordinated-5]]
| + | |
| Structural highlights
Function
UNC5D_RAT Receptor for the netrin NTN4 that promotes neuronal cell survival. Plays a role in cell-cell adhesion and cell guidance. Receptor for netrin involved in cell migration. Plays a role in axon guidance by mediating axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. May play a role in apoptosis in response to DNA damage. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand (By similarity). Mediates cell-cell adhesion via its interaction with FLRT3 on an adjacent cell (By similarity).[UniProtKB:Q6UXZ4][UniProtKB:Q8K1S2]
Publication Abstract from PubMed
Latrophilin adhesion-GPCRs (Lphn1-3 or ADGRL1-3) and Unc5 cell guidance receptors (Unc5A-D) interact with FLRT proteins (FLRT1-3), thereby promoting cell adhesion and repulsion, respectively. How the three proteins interact and function simultaneously is poorly understood. We show that Unc5D interacts with FLRT2 in cis, controlling cell adhesion in response to externally presented Lphn3. The ectodomains of the three proteins bind cooperatively. Crystal structures of the ternary complex formed by the extracellular domains reveal that Lphn3 dimerizes when bound to FLRT2:Unc5, resulting in a stoichiometry of 1:1:2 (FLRT2:Unc5D:Lphn3). This 1:1:2 complex further dimerizes to form a larger 'super-complex' (2:2:4), using a previously undescribed binding motif in the Unc5D TSP1 domain. Molecular dynamics simulations, point-directed mutagenesis and mass spectrometry demonstrate the stability and molecular properties of these complexes. Our data exemplify how receptors increase their functional repertoire by forming different context-dependent higher-order complexes.
Super-complexes of adhesion GPCRs and neural guidance receptors.,Jackson VA, Mehmood S, Chavent M, Roversi P, Carrasquero M, Del Toro D, Seyit-Bremer G, Ranaivoson FM, Comoletti D, Sansom MS, Robinson CV, Klein R, Seiradake E Nat Commun. 2016 Apr 19;7:11184. doi: 10.1038/ncomms11184. PMID:27091502[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jackson VA, Mehmood S, Chavent M, Roversi P, Carrasquero M, Del Toro D, Seyit-Bremer G, Ranaivoson FM, Comoletti D, Sansom MS, Robinson CV, Klein R, Seiradake E. Super-complexes of adhesion GPCRs and neural guidance receptors. Nat Commun. 2016 Apr 19;7:11184. doi: 10.1038/ncomms11184. PMID:27091502 doi:http://dx.doi.org/10.1038/ncomms11184
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