7eq1: Difference between revisions

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==GPR114-Gs-scFv16 complex==
==GPR114-Gs-scFv16 complex==
<StructureSection load='7eq1' size='340' side='right'caption='[[7eq1]]' scene=''>
<StructureSection load='7eq1' size='340' side='right'caption='[[7eq1]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EQ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EQ1 FirstGlance]. <br>
<table><tr><td colspan='2'>[[7eq1]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] 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=7EQ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EQ1 FirstGlance]. <br>
</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=7eq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eq1 OCA], [https://pdbe.org/7eq1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eq1 RCSB], [https://www.ebi.ac.uk/pdbsum/7eq1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eq1 ProSAT]</span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#8491;</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=7eq1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7eq1 OCA], [https://pdbe.org/7eq1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7eq1 RCSB], [https://www.ebi.ac.uk/pdbsum/7eq1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7eq1 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GBG2_BOVIN GBG2_BOVIN] 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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Adhesion G-protein-coupled receptors (aGPCRs) are important for organogenesis, neurodevelopment, reproduction and other processes(1-6). Many aGPCRs are activated by a conserved internal (tethered) agonist sequence known as the Stachel sequence(7-12). Here, we report the cryogenic electron microscopy (cryo-EM) structures of two aGPCRs in complex with G(s): GPR133 and GPR114. The structures indicate that the Stachel sequences of both receptors assume an alpha-helical-bulge-beta-sheet structure and insert into a binding site formed by the transmembrane domain (TMD). A hydrophobic interaction motif (HIM) within the Stachel sequence mediates most of the intramolecular interactions with the TMD. Combined with the cryo-EM structures, biochemical characterization of the HIM motif provides insight into the cross-reactivity and selectivity of the Stachel sequences. Two interconnected mechanisms, the sensing of Stachel sequences by the conserved 'toggle switch' W(6.53) and the constitution of a hydrogen-bond network formed by Q(7.49)/Y(7.49) and the P(6.47)/V(6.47)phiphiG(6.50) motif (phi indicates a hydrophobic residue), are important in Stachel sequence-mediated receptor activation and G(s) coupling. Notably, this network stabilizes kink formation in TM helices 6 and 7 (TM6 and TM7, respectively). A common G(s)-binding interface is observed between the two aGPCRs, and GPR114 has an extended TM7 that forms unique interactions with G(s). Our structures reveal the detailed mechanisms of aGPCR activation by Stachel sequences and their G(s) coupling.
Structural basis for the tethered peptide activation of adhesion GPCRs.,Ping YQ, Xiao P, Yang F, Zhao RJ, Guo SC, Yan X, Wu X, Zhang C, Lu Y, Zhao F, Zhou F, Xi YT, Yin W, Liu FZ, He DF, Zhang DL, Zhu ZL, Jiang Y, Du L, Feng SQ, Schoneberg T, Liebscher I, Xu HE, Sun JP Nature. 2022 Apr;604(7907):763-770. doi: 10.1038/s41586-022-04619-y. Epub 2022 , Apr 13. PMID:35418678<ref>PMID:35418678</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7eq1" style="background-color:#fffaf0;"></div>
==See Also==
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Bos taurus]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Synthetic construct]]
[[Category: Ping Y]]
[[Category: Ping Y]]

Latest revision as of 16:34, 6 November 2024

GPR114-Gs-scFv16 complexGPR114-Gs-scFv16 complex

Structural highlights

7eq1 is a 5 chain structure with sequence from Bos taurus, Homo sapiens, Rattus norvegicus and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.3Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GBG2_BOVIN 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.

Publication Abstract from PubMed

Adhesion G-protein-coupled receptors (aGPCRs) are important for organogenesis, neurodevelopment, reproduction and other processes(1-6). Many aGPCRs are activated by a conserved internal (tethered) agonist sequence known as the Stachel sequence(7-12). Here, we report the cryogenic electron microscopy (cryo-EM) structures of two aGPCRs in complex with G(s): GPR133 and GPR114. The structures indicate that the Stachel sequences of both receptors assume an alpha-helical-bulge-beta-sheet structure and insert into a binding site formed by the transmembrane domain (TMD). A hydrophobic interaction motif (HIM) within the Stachel sequence mediates most of the intramolecular interactions with the TMD. Combined with the cryo-EM structures, biochemical characterization of the HIM motif provides insight into the cross-reactivity and selectivity of the Stachel sequences. Two interconnected mechanisms, the sensing of Stachel sequences by the conserved 'toggle switch' W(6.53) and the constitution of a hydrogen-bond network formed by Q(7.49)/Y(7.49) and the P(6.47)/V(6.47)phiphiG(6.50) motif (phi indicates a hydrophobic residue), are important in Stachel sequence-mediated receptor activation and G(s) coupling. Notably, this network stabilizes kink formation in TM helices 6 and 7 (TM6 and TM7, respectively). A common G(s)-binding interface is observed between the two aGPCRs, and GPR114 has an extended TM7 that forms unique interactions with G(s). Our structures reveal the detailed mechanisms of aGPCR activation by Stachel sequences and their G(s) coupling.

Structural basis for the tethered peptide activation of adhesion GPCRs.,Ping YQ, Xiao P, Yang F, Zhao RJ, Guo SC, Yan X, Wu X, Zhang C, Lu Y, Zhao F, Zhou F, Xi YT, Yin W, Liu FZ, He DF, Zhang DL, Zhu ZL, Jiang Y, Du L, Feng SQ, Schoneberg T, Liebscher I, Xu HE, Sun JP Nature. 2022 Apr;604(7907):763-770. doi: 10.1038/s41586-022-04619-y. Epub 2022 , Apr 13. PMID:35418678[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Ping YQ, Xiao P, Yang F, Zhao RJ, Guo SC, Yan X, Wu X, Zhang C, Lu Y, Zhao F, Zhou F, Xi YT, Yin W, Liu FZ, He DF, Zhang DL, Zhu ZL, Jiang Y, Du L, Feng SQ, Schöneberg T, Liebscher I, Xu HE, Sun JP. Structural basis for the tethered peptide activation of adhesion GPCRs. Nature. 2022 Apr;604(7907):763-770. PMID:35418678 doi:10.1038/s41586-022-04619-y

7eq1, resolution 3.30Å

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