7wu5: Difference between revisions
No edit summary |
No edit summary |
||
| (2 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Cryo-EM structure of the adhesion GPCR ADGRF1(H565A/T567A) in complex with miniGi== | |||
<StructureSection load='7wu5' size='340' side='right'caption='[[7wu5]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7wu5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7WU5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7WU5 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]] 3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=K6G:[(2~{R})-2-oxidanyl-3-[oxidanyl-[2-(trimethyl-$l^{4}-azanyl)ethoxy]phosphoryl]oxy-propyl]+hexadecanoate'>K6G</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=7wu5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7wu5 OCA], [https://pdbe.org/7wu5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7wu5 RCSB], [https://www.ebi.ac.uk/pdbsum/7wu5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7wu5 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Adhesion G protein-coupled receptors (aGPCRs) are essential for a variety of physiological processes such as immune responses, organ development, cellular communication, proliferation and homeostasis(1-7). An intrinsic manner of activation that involves a tethered agonist in the N-terminal region of the receptor has been proposed for the aGPCRs(8,9), but its molecular mechanism remains elusive. Here we report the G protein-bound structures of ADGRD1 and ADGRF1, which exhibit many unique features with regard to the tethered agonism. The stalk region that proceeds the first transmembrane helix acts as the tethered agonist by forming extensive interactions with the transmembrane domain; these interactions are mostly conserved in ADGRD1 and ADGRF1, suggesting that a common stalk-transmembrane domain interaction pattern is shared by members of the aGPCR family. A similar stalk binding mode is observed in the structure of autoproteolysis-deficient ADGRF1, supporting a cleavage-independent manner of receptor activation. The stalk-induced activation is facilitated by a cascade of inter-helix interaction cores that are conserved in positions but show sequence variability in these two aGPCRs. Furthermore, the intracellular region of ADGRF1 contains a specific lipid-binding site, which proves to be functionally important and may serve as the recognition site for the previously discovered endogenous ADGRF1 ligand synaptamide. These findings highlight the diversity and complexity of the signal transduction mechanisms of the aGPCRs. | |||
Structural basis of tethered agonism of the adhesion GPCRs ADGRD1 and ADGRF1.,Qu X, Qiu N, Wang M, Zhang B, Du J, Zhong Z, Xu W, Chu X, Ma L, Yi C, Han S, Shui W, Zhao Q, Wu B Nature. 2022 Apr;604(7907):779-785. doi: 10.1038/s41586-022-04580-w. Epub 2022 , Apr 13. PMID:35418679<ref>PMID:35418679</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7wu5" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Transducin 3D structures|Transducin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Qiu N]] | |||
[[Category: Qu X]] | |||
[[Category: Wang M]] | |||
[[Category: Wu B]] | |||
[[Category: Zhao Q]] | |||
Latest revision as of 12:19, 17 October 2024
Cryo-EM structure of the adhesion GPCR ADGRF1(H565A/T567A) in complex with miniGiCryo-EM structure of the adhesion GPCR ADGRF1(H565A/T567A) in complex with miniGi
Structural highlights
Publication Abstract from PubMedAdhesion G protein-coupled receptors (aGPCRs) are essential for a variety of physiological processes such as immune responses, organ development, cellular communication, proliferation and homeostasis(1-7). An intrinsic manner of activation that involves a tethered agonist in the N-terminal region of the receptor has been proposed for the aGPCRs(8,9), but its molecular mechanism remains elusive. Here we report the G protein-bound structures of ADGRD1 and ADGRF1, which exhibit many unique features with regard to the tethered agonism. The stalk region that proceeds the first transmembrane helix acts as the tethered agonist by forming extensive interactions with the transmembrane domain; these interactions are mostly conserved in ADGRD1 and ADGRF1, suggesting that a common stalk-transmembrane domain interaction pattern is shared by members of the aGPCR family. A similar stalk binding mode is observed in the structure of autoproteolysis-deficient ADGRF1, supporting a cleavage-independent manner of receptor activation. The stalk-induced activation is facilitated by a cascade of inter-helix interaction cores that are conserved in positions but show sequence variability in these two aGPCRs. Furthermore, the intracellular region of ADGRF1 contains a specific lipid-binding site, which proves to be functionally important and may serve as the recognition site for the previously discovered endogenous ADGRF1 ligand synaptamide. These findings highlight the diversity and complexity of the signal transduction mechanisms of the aGPCRs. Structural basis of tethered agonism of the adhesion GPCRs ADGRD1 and ADGRF1.,Qu X, Qiu N, Wang M, Zhang B, Du J, Zhong Z, Xu W, Chu X, Ma L, Yi C, Han S, Shui W, Zhao Q, Wu B Nature. 2022 Apr;604(7907):779-785. doi: 10.1038/s41586-022-04580-w. Epub 2022 , Apr 13. PMID:35418679[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||