8dcs
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[8dcs]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Lama_glama Lama glama] and [https://en.wikipedia.org/wiki/Meleagris_gallopavo Meleagris gallopavo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DCS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DCS FirstGlance]. <br> | <table><tr><td colspan='2'>[[8dcs]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Lama_glama Lama glama] and [https://en.wikipedia.org/wiki/Meleagris_gallopavo Meleagris gallopavo]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DCS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DCS FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P32:4-{[(2S)-3-(TERT-BUTYLAMINO)-2-HYDROXYPROPYL]OXY}-3H-INDOLE-2-CARBONITRILE'>P32</scene></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]] 2.5Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P32:4-{[(2S)-3-(TERT-BUTYLAMINO)-2-HYDROXYPROPYL]OXY}-3H-INDOLE-2-CARBONITRILE'>P32</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=8dcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dcs OCA], [https://pdbe.org/8dcs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dcs RCSB], [https://www.ebi.ac.uk/pdbsum/8dcs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dcs ProSAT]</span></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=8dcs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dcs OCA], [https://pdbe.org/8dcs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dcs RCSB], [https://www.ebi.ac.uk/pdbsum/8dcs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dcs ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | + | [https://www.uniprot.org/uniprot/GBB1_BOVIN GBB1_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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| - | G-protein-coupled receptors (GPCRs) receive signals from ligands with different efficacies, and transduce to heterotrimeric G-proteins to generate different degrees of physiological responses. Previous studies revealed how ligands with different efficacies activate GPCRs. Here, we investigate how a GPCR activates G-proteins upon binding ligands with different efficacies. We report the cryo-EM structures of | + | G-protein-coupled receptors (GPCRs) receive signals from ligands with different efficacies, and transduce to heterotrimeric G-proteins to generate different degrees of physiological responses. Previous studies revealed how ligands with different efficacies activate GPCRs. Here, we investigate how a GPCR activates G-proteins upon binding ligands with different efficacies. We report the cryo-EM structures of beta(1)-adrenergic receptor (beta(1)-AR) in complex with Gs (Galpha(s)Gbeta(1)Ggamma(2)) and a partial agonist or a very weak partial agonist, and compare them to the beta(1)-AR-Gs structure in complex with a full agonist. Analyses reveal similar overall complex architecture, with local conformational differences. Cellular functional studies with mutations of beta(1)-AR residues show effects on the cellular signaling from beta(1)-AR to the cAMP response initiated by the three different ligands, with residue-specific functional differences. Biochemical investigations uncover that the intermediate state complex comprising beta(1)-AR and nucleotide-free Gs is more stable when binding a full agonist than a partial agonist. Molecular dynamics simulations support the local conformational flexibilities and different stabilities among the three complexes. These data provide insights into the ligand efficacy in the activation of GPCRs and G-proteins. |
| - | Structures of | + | Structures of beta(1)-adrenergic receptor in complex with Gs and ligands of different efficacies.,Su M, Paknejad N, Zhu L, Wang J, Do HN, Miao Y, Liu W, Hite RK, Huang XY Nat Commun. 2022 Jul 14;13(1):4095. doi: 10.1038/s41467-022-31823-1. PMID:35835792<ref>PMID:35835792</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 8dcs" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 8dcs" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Transducin 3D structures|Transducin 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Cryo-EM structure of cyanopindolol-bound beta1-adrenergic receptor in complex with heterotrimeric Gs-protein
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