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==Structural Basis of the Activation of Heterotrimeric Gs-protein by Isoproterenol-bound Beta1-Adrenergic Receptor==
<StructureSection load='7jjo' size='340' side='right'caption='[[7jjo]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7jjo]] 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=7JJO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7JJO 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5FW:ISOPRENALINE'>5FW</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=7jjo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7jjo OCA], [https://pdbe.org/7jjo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7jjo RCSB], [https://www.ebi.ac.uk/pdbsum/7jjo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7jjo ProSAT]</span></td></tr>
</table>
== 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.
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== Publication Abstract from PubMed ==
Cardiac disease remains the leading cause of morbidity and mortality worldwide. The beta1-adrenergic receptor (beta1-AR) is a major regulator of cardiac functions and is downregulated in the majority of heart failure cases. A key physiological process is the activation of heterotrimeric G-protein Gs by beta1-ARs, leading to increased heart rate and contractility. Here, we use cryo-electron microscopy and functional studies to investigate the molecular mechanism by which beta1-AR activates Gs. We find that the tilting of alpha5-helix breaks a hydrogen bond between the sidechain of His373 in the C-terminal alpha5-helix and the backbone carbonyl of Arg38 in the N-terminal alphaN-helix of Galphas. Together with the disruption of another interacting network involving Gln59 in the alpha1-helix, Ala352 in the beta6-alpha5 loop, and Thr355 in the alpha5-helix, these conformational changes might lead to the deformation of the GDP-binding pocket. Our data provide molecular insights into the activation of G-proteins by G-protein-coupled receptors.

Structural Basis of the Activation of Heterotrimeric Gs-Protein by Isoproterenol-Bound beta1-Adrenergic Receptor.,Su M, Zhu L, Zhang Y, Paknejad N, Dey R, Huang J, Lee MY, Williams D, Jordan KD, Eng ET, Ernst OP, Meyerson JR, Hite RK, Walz T, Liu W, Huang XY Mol Cell. 2020 Oct 1;80(1):59-71.e4. doi: 10.1016/j.molcel.2020.08.001. Epub 2020, Aug 19. PMID:32818430<ref>PMID:32818430</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7jjo" style="background-color:#fffaf0;"></div>

==See Also==
*[[Adrenergic receptor 3D structures|Adrenergic receptor 3D structures]]
*[[Antibody 3D structures|Antibody 3D structures]]
*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Meleagris gallopavo]]
[[Category: Dey R]]
[[Category: Eng ET]]
[[Category: Ernst OP]]
[[Category: Hite RK]]
[[Category: Huang J]]
[[Category: Huang XY]]
[[Category: Jordan KD]]
[[Category: Lee MY]]
[[Category: Liu W]]
[[Category: Meyerson JR]]
[[Category: Paknejad N]]
[[Category: Su M]]
[[Category: Walz T]]
[[Category: Williams D]]
[[Category: Zhang Y]]
[[Category: Zhu L]]