8vti: Difference between revisions

New page: '''Unreleased structure''' The entry 8vti is ON HOLD Authors: Description: Category: Unreleased Structures
 
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'''Unreleased structure'''


The entry 8vti is ON HOLD
==Latrophilin-3 (ADGRL3) HormR and GAIN domains in the context of the holoreceptor==
<StructureSection load='8vti' size='340' side='right'caption='[[8vti]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8vti]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8VTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VTI FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.9&#8491;</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'>[https://proteopedia.org/fgij/fg.htm?mol=8vti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vti OCA], [https://pdbe.org/8vti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vti RCSB], [https://www.ebi.ac.uk/pdbsum/8vti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vti ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AGRL3_HUMAN AGRL3_HUMAN] 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:26235030). Plays a role in the development of glutamatergic synapses in the cortex. Important in determining the connectivity rates between the principal neurons in the cortex.[UniProtKB:Q80TS3]<ref>PMID:26235030</ref>
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== Publication Abstract from PubMed ==
Adhesion G Protein-Coupled Receptors (aGPCRs) are key cell-adhesion molecules involved in numerous physiological functions. aGPCRs have large multi-domain extracellular regions (ECRs) containing a conserved GAIN domain that precedes their seven-pass transmembrane domain (7TM). Ligand binding and mechanical force applied on the ECR regulate receptor function. However, how the ECR communicates with the 7TM remains elusive, because the relative orientation and dynamics of the ECR and 7TM within a holoreceptor is unclear. Here, we describe the cryo-EM reconstruction of an aGPCR, Latrophilin3/ADGRL3, and reveal that the GAIN domain adopts a parallel orientation to the transmembrane region and has constrained movement. Single-molecule FRET experiments unveil three slow-exchanging FRET states of the ECR relative to the transmembrane region within the holoreceptor. GAIN-targeted antibodies, and cancer-associated mutations at the GAIN-7TM interface, alter FRET states, cryo-EM conformations, and receptor signaling. Altogether, this data demonstrates conformational and functional coupling between the ECR and 7TM, suggesting an ECR-mediated mechanism for aGPCR activation.


Authors:  
Conformational coupling between extracellular and transmembrane domains modulates holo-adhesion GPCR function.,Kordon SP, Cechova K, Bandekar SJ, Leon K, Dutka P, Siffer G, Kossiakoff AA, Vafabakhsh R, Arac D Nat Commun. 2024 Dec 4;15(1):10545. doi: 10.1038/s41467-024-54836-4. PMID:39627215<ref>PMID:39627215</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 8vti" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Arac D]]
[[Category: Bandekar SJ]]
[[Category: Kordon SP]]

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