4v2e: Difference between revisions
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==FLRT3 LRR domain== | ==FLRT3 LRR domain== | ||
<StructureSection load='4v2e' size='340' side='right' caption='[[4v2e]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='4v2e' size='340' side='right'caption='[[4v2e]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4v2e]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4V2E OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4v2e]] 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=4V2E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4V2E FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4v2e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4v2e OCA], [https://pdbe.org/4v2e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4v2e RCSB], [https://www.ebi.ac.uk/pdbsum/4v2e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4v2e ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/FLRT3_MOUSE FLRT3_MOUSE] Functions in cell-cell adhesion, cell migration and axon guidance, exerting an attractive or repulsive role depending on its interaction partners (PubMed:19056886, PubMed:25374360). Plays a role in the spatial organization of brain neurons (PubMed:25374360). Plays a role in vascular development in the retina (PubMed:25374360). Plays a role in cell-cell adhesion via its interaction with ADGRL3 and probably also other latrophilins that are expressed at the surface of adjacent cells (PubMed:22405201, PubMed:25374360). Interaction with the intracellular domain of ROBO1 mediates axon attraction towards cells expressing NTN1 (PubMed:24560577). Mediates axon growth cone collapse and plays a repulsive role in neuron guidance via its interaction with UNC5B, and possibly also other UNC-5 family members (PubMed:21673655, PubMed:25374360). Promotes neurite outgrowth (in vitro) (By similarity). Mediates cell-cell contacts that promote an increase both in neurite number and in neurite length (By similarity). Plays a role in the regulation of the density of glutamaergic synapses (PubMed:22405201). Plays a role in fibroblast growth factor-mediated signaling cascades (PubMed:16872596). Required for normal morphogenesis during embryonic development, but not for normal embryonic patterning (PubMed:19056886). Required for normal ventral closure, headfold fusion and definitive endoderm migration during embryonic development (PubMed:18448090). Required for the formation of a normal basement membrane and the maintenance of a normal anterior visceral endoderm during embryonic development (PubMed:19056886).[UniProtKB:B1H234]<ref>PMID:16872596</ref> <ref>PMID:18448090</ref> <ref>PMID:19056886</ref> <ref>PMID:21673655</ref> <ref>PMID:22405201</ref> <ref>PMID:24560577</ref> <ref>PMID:25374360</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
FLRTs are broadly expressed proteins with the unique property of acting as homophilic cell adhesion molecules and as heterophilic repulsive ligands of Unc5/Netrin receptors. How these functions direct cell behavior and the molecular mechanisms involved remain largely unclear. Here we use X-ray crystallography to reveal the distinct structural bases for FLRT-mediated cell adhesion and repulsion in neurons. We apply this knowledge to elucidate FLRT functions during cortical development. We show that FLRTs regulate both the radial migration of pyramidal neurons, as well as their tangential spread. Mechanistically, radial migration is controlled by repulsive FLRT2-Unc5D interactions, while spatial organization in the tangential axis involves adhesive FLRT-FLRT interactions. Further, we show that the fundamental mechanisms of FLRT adhesion and repulsion are conserved between neurons and vascular endothelial cells. Our results reveal FLRTs as powerful guidance factors with structurally encoded repulsive and adhesive surfaces. | |||
FLRT structure: balancing repulsion and cell adhesion in cortical and vascular development.,Seiradake E, del Toro D, Nagel D, Cop F, Hartl R, Ruff T, Seyit-Bremer G, Harlos K, Border EC, Acker-Palmer A, Jones EY, Klein R Neuron. 2014 Oct 22;84(2):370-85. doi: 10.1016/j.neuron.2014.10.008. Epub 2014, Oct 22. PMID:25374360<ref>PMID:25374360</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4v2e" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Acker-Palmer | [[Category: Large Structures]] | ||
[[Category: Border | [[Category: Mus musculus]] | ||
[[Category: Cop | [[Category: Acker-Palmer A]] | ||
[[Category: Haertl | [[Category: Border EC]] | ||
[[Category: Harlos | [[Category: Cop F]] | ||
[[Category: Jones | [[Category: Haertl R]] | ||
[[Category: Klein | [[Category: Harlos K]] | ||
[[Category: Nagel | [[Category: Jones EY]] | ||
[[Category: Ruff | [[Category: Klein R]] | ||
[[Category: Seiradake | [[Category: Nagel D]] | ||
[[Category: Seyit-Bremer | [[Category: Ruff T]] | ||
[[Category: Toro | [[Category: Seiradake E]] | ||
[[Category: Seyit-Bremer G]] | |||
[[Category: Del Toro D]] | |||
Latest revision as of 13:39, 10 January 2024
FLRT3 LRR domainFLRT3 LRR domain
Structural highlights
FunctionFLRT3_MOUSE Functions in cell-cell adhesion, cell migration and axon guidance, exerting an attractive or repulsive role depending on its interaction partners (PubMed:19056886, PubMed:25374360). Plays a role in the spatial organization of brain neurons (PubMed:25374360). Plays a role in vascular development in the retina (PubMed:25374360). Plays a role in cell-cell adhesion via its interaction with ADGRL3 and probably also other latrophilins that are expressed at the surface of adjacent cells (PubMed:22405201, PubMed:25374360). Interaction with the intracellular domain of ROBO1 mediates axon attraction towards cells expressing NTN1 (PubMed:24560577). Mediates axon growth cone collapse and plays a repulsive role in neuron guidance via its interaction with UNC5B, and possibly also other UNC-5 family members (PubMed:21673655, PubMed:25374360). Promotes neurite outgrowth (in vitro) (By similarity). Mediates cell-cell contacts that promote an increase both in neurite number and in neurite length (By similarity). Plays a role in the regulation of the density of glutamaergic synapses (PubMed:22405201). Plays a role in fibroblast growth factor-mediated signaling cascades (PubMed:16872596). Required for normal morphogenesis during embryonic development, but not for normal embryonic patterning (PubMed:19056886). Required for normal ventral closure, headfold fusion and definitive endoderm migration during embryonic development (PubMed:18448090). Required for the formation of a normal basement membrane and the maintenance of a normal anterior visceral endoderm during embryonic development (PubMed:19056886).[UniProtKB:B1H234][1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedFLRTs are broadly expressed proteins with the unique property of acting as homophilic cell adhesion molecules and as heterophilic repulsive ligands of Unc5/Netrin receptors. How these functions direct cell behavior and the molecular mechanisms involved remain largely unclear. Here we use X-ray crystallography to reveal the distinct structural bases for FLRT-mediated cell adhesion and repulsion in neurons. We apply this knowledge to elucidate FLRT functions during cortical development. We show that FLRTs regulate both the radial migration of pyramidal neurons, as well as their tangential spread. Mechanistically, radial migration is controlled by repulsive FLRT2-Unc5D interactions, while spatial organization in the tangential axis involves adhesive FLRT-FLRT interactions. Further, we show that the fundamental mechanisms of FLRT adhesion and repulsion are conserved between neurons and vascular endothelial cells. Our results reveal FLRTs as powerful guidance factors with structurally encoded repulsive and adhesive surfaces. FLRT structure: balancing repulsion and cell adhesion in cortical and vascular development.,Seiradake E, del Toro D, Nagel D, Cop F, Hartl R, Ruff T, Seyit-Bremer G, Harlos K, Border EC, Acker-Palmer A, Jones EY, Klein R Neuron. 2014 Oct 22;84(2):370-85. doi: 10.1016/j.neuron.2014.10.008. Epub 2014, Oct 22. PMID:25374360[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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