9e7r: Difference between revisions

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'''Unreleased structure'''


The entry 9e7r is ON HOLD  until Paper Publication
==CryoEM structure of PAR2 with GB88==
<StructureSection load='9e7r' size='340' side='right'caption='[[9e7r]], [[Resolution|resolution]] 3.18&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9e7r]] is a 5 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=9E7R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9E7R 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]] 3.18&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1BF3:N-[(2S)-3-cyclohexyl-1-{[(2S,3S)-3-methyl-1-oxo-1-(spiro[indene-1,4-piperidin]-1-yl)pentan-2-yl]amino}-1-oxopropan-2-yl]-1,2-oxazole-5-carboxamide'>A1BF3</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=9e7r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9e7r OCA], [https://pdbe.org/9e7r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9e7r RCSB], [https://www.ebi.ac.uk/pdbsum/9e7r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9e7r ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GBG2_HUMAN GBG2_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Members of the proteinase-activated receptor (PAR) subfamily of G protein-coupled receptors (GPCRs) play critical roles in processes like hemostasis, thrombosis, development, wound healing, inflammation, and cancer progression. Comprising PAR1-PAR4, these receptors are specifically activated by protease cleavage at their extracellular amino terminus, revealing a 'tethered ligand' that self-activates the receptor. This triggers complex intracellular signaling via G proteins and beta-arrestins, linking external protease signals to cellular functions. To date, direct structural visualization of these ligand-receptor complexes has been limited. Here, we present structural snapshots of activated PAR1 and PAR2 bound to their endogenous tethered ligands, revealing a shallow and constricted orthosteric binding pocket. Comparisons with antagonist-bound structures show minimal conformational changes in the TM6 helix and larger movements of TM7 upon activation. These findings reveal a common activation mechanism for PAR1 and PAR2, highlighting critical residues involved in ligand recognition. Additionally, the structure of PAR2 bound to a pathway selective antagonist, GB88, demonstrates how potent orthosteric engagement can be achieved by a small molecule mimicking the endogenous tethered ligand's interactions.


Authors: Lyu, X., Lyu, Z., Malyutin, A.G., McGrath, A.P., Kang, Y.
Structural basis for the activation of proteinase-activated receptors PAR1 and PAR2.,Lyu Z, Lyu X, Malyutin AG, Xia G, Carney D, Alves VM, Falk M, Arora N, Zou H, McGrath AP, Kang Y Nat Commun. 2025 Apr 26;16(1):3931. doi: 10.1038/s41467-025-59138-x. PMID:40287415<ref>PMID:40287415</ref>


Description: CryoEM structure of PAR2 with GB88
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Kang, Y]]
<div class="pdbe-citations 9e7r" style="background-color:#fffaf0;"></div>
[[Category: Malyutin, A.G]]
== References ==
[[Category: Mcgrath, A.P]]
<references/>
[[Category: Lyu, Z]]
__TOC__
[[Category: Lyu, X]]
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kang Y]]
[[Category: Lyu X]]
[[Category: Lyu Z]]
[[Category: Malyutin AG]]
[[Category: McGrath AP]]
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