6v55: Difference between revisions
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==Full extracellular region of zebrafish Gpr126/Adgrg6== | |||
<StructureSection load='6v55' size='340' side='right'caption='[[6v55]], [[Resolution|resolution]] 2.38Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6v55]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V55 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V55 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.38Å</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6v55 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v55 OCA], [https://pdbe.org/6v55 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v55 RCSB], [https://www.ebi.ac.uk/pdbsum/6v55 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v55 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/AGRG6_DANRE AGRG6_DANRE] G-protein coupled receptor which is activated by type IV collagen, a major constituent of the basement membrane. Couples to G(i)-proteins as well as G(s)-proteins (PubMed:25118328). Essential for normal differentiation of promyelinating Schwann cells and for normal myelination of axons (PubMed:19745155). Plays also a role in inner ear development (PubMed:24067352).[UniProtKB:Q86SQ4]<ref>PMID:19745155</ref> <ref>PMID:24067352</ref> <ref>PMID:25118328</ref> Plays an important role in heart development (PubMed:24082093). Necessary and sufficient for axon sorting by Schwann cells independently of the ADGRG6-CTF (PubMed:25695270).<ref>PMID:24082093</ref> <ref>PMID:25695270</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Many drugs target the extracellular regions (ECRs) of cell-surface receptors. The large and alternatively-spliced ECRs of adhesion G protein-coupled receptors (aGPCRs) have key functions in diverse biological processes including neurodevelopment, embryogenesis, and tumorigenesis. However, their structures and mechanisms of action remain unclear, hampering drug development. The aGPCR Gpr126/Adgrg6 regulates Schwann cell myelination, ear canal formation, and heart development; and GPR126 mutations cause myelination defects in human. Here, we determine the structure of the complete zebrafish Gpr126 ECR and reveal five domains including a previously unknown domain. Strikingly, the Gpr126 ECR adopts a closed conformation that is stabilized by an alternatively spliced linker and a conserved calcium-binding site. Alternative splicing regulates ECR conformation and receptor signaling, while mutagenesis of the calcium-binding site abolishes Gpr126 function in vivo. These results demonstrate that Gpr126 ECR utilizes a multi-faceted dynamic approach to regulate receptor function and provide relevant insights for ECR-targeted drug design. | |||
Structural basis for adhesion G protein-coupled receptor Gpr126 function.,Leon K, Cunningham RL, Riback JA, Feldman E, Li J, Sosnick TR, Zhao M, Monk KR, Arac D Nat Commun. 2020 Jan 10;11(1):194. doi: 10.1038/s41467-019-14040-1. PMID:31924782<ref>PMID:31924782</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6v55" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Danio rerio]] | |||
[[Category: Large Structures]] | |||
[[Category: Arac D]] | |||
[[Category: Leon K]] | |||