5g53

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==Structure of the adenosine A2A receptor bound to an engineered G protein==
==Structure of the adenosine A2A receptor bound to an engineered G protein==
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<StructureSection load='5g53' size='340' side='right' caption='[[5g53]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
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<StructureSection load='5g53' size='340' side='right'caption='[[5g53]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5g53]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5G53 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5G53 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5g53]] 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=5G53 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5G53 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=NEC:N-ETHYL-5-CARBOXAMIDO+ADENOSINE'>NEC</scene>, <scene name='pdbligand=SOG:2-HYDROXYMETHYL-6-OCTYLSULFANYL-TETRAHYDRO-PYRAN-3,4,5-TRIOL'>SOG</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.4&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5g53 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g53 OCA], [http://pdbe.org/5g53 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5g53 RCSB], [http://www.ebi.ac.uk/pdbsum/5g53 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5g53 ProSAT]</span></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=NEC:N-ETHYL-5-CARBOXAMIDO+ADENOSINE'>NEC</scene>, <scene name='pdbligand=SOG:2-HYDROXYMETHYL-6-OCTYLSULFANYL-TETRAHYDRO-PYRAN-3,4,5-TRIOL'>SOG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5g53 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5g53 OCA], [https://pdbe.org/5g53 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5g53 RCSB], [https://www.ebi.ac.uk/pdbsum/5g53 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5g53 ProSAT]</span></td></tr>
</table>
</table>
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== Disease ==
 
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[[http://www.uniprot.org/uniprot/GNAS2_HUMAN GNAS2_HUMAN]] Pseudopseudohypoparathyroidism;Pseudohypoparathyroidism type 1A;Progressive osseous heteroplasia;Polyostotic fibrous dysplasia;Monostotic fibrous dysplasia;Pseudohypoparathyroidism type 1C;Pseudohypoparathyroidism type 1B;McCune-Albright syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Most affected individuals have defects in methylation of the gene. In some cases microdeletions involving the STX16 appear to cause loss of methylation at exon A/B of GNAS, resulting in PHP1B. Paternal uniparental isodisomy have also been observed. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
 
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/AA2AR_HUMAN AA2AR_HUMAN]] Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. [[http://www.uniprot.org/uniprot/GNAS2_HUMAN GNAS2_HUMAN]] Guanine nucleotide-binding proteins (G proteins) function as transducers in numerous signaling pathways controlled by G protein-coupled receptors (GPCRs) (PubMed:17110384). Signaling involves the activation of adenylyl cyclases, resulting in increased levels of the signaling molecule cAMP (PubMed:26206488, PubMed:8702665). GNAS functions downstream of several GPCRs, including beta-adrenergic receptors (PubMed:21488135). Stimulates the Ras signaling pathway via RAPGEF2 (PubMed:12391161).<ref>PMID:12391161</ref> <ref>PMID:17110384</ref> <ref>PMID:21488135</ref> <ref>PMID:26206488</ref> <ref>PMID:8702665</ref>
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[https://www.uniprot.org/uniprot/AA2AR_HUMAN AA2AR_HUMAN] Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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Adenosine receptors and beta-adrenoceptors are G-protein-coupled receptors (GPCRs) that activate intracellular G proteins on binding the agonists adenosine or noradrenaline, respectively. GPCRs have similar structures consisting of seven transmembrane helices that contain well-conserved sequence motifs, indicating that they are probably activated by a common mechanism. Recent structures of beta-adrenoceptors highlight residues in transmembrane region 5 that initially bind specifically to agonists rather than to antagonists, indicating that these residues have an important role in agonist-induced activation of receptors. Here we present two crystal structures of the thermostabilized human adenosine A(2A) receptor (A(2A)R-GL31) bound to its endogenous agonist adenosine and the synthetic agonist NECA. The structures represent an intermediate conformation between the inactive and active states, because they share all the features of GPCRs that are thought to be in a fully activated state, except that the cytoplasmic end of transmembrane helix 6 partially occludes the G-protein-binding site. The adenine substituent of the agonists binds in a similar fashion to the chemically related region of the inverse agonist ZM241385 (ref. 8). Both agonists contain a ribose group, not found in ZM241385, which extends deep into the ligand-binding pocket where it makes polar interactions with conserved residues in H7 (Ser 277(7.42) and His 278(7.43); superscripts refer to Ballesteros-Weinstein numbering) and non-polar interactions with residues in H3. In contrast, the inverse agonist ZM241385 does not interact with any of these residues and comparison with the agonist-bound structures indicates that ZM241385 sterically prevents the conformational change in H5 and therefore it acts as an inverse agonist. Comparison of the agonist-bound structures of A(2A)R with the agonist-bound structures of beta-adrenoceptors indicates that the contraction of the ligand-binding pocket caused by the inward motion of helices 3, 5 and 7 may be a common feature in the activation of all GPCRs.
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G-protein-coupled receptors (GPCRs) are essential components of the signalling network throughout the body. To understand the molecular mechanism of G-protein-mediated signalling, solved structures of receptors in inactive conformations and in the active conformation coupled to a G protein are necessary. Here we present the structure of the adenosine A(2A) receptor (A(2A)R) bound to an engineered G protein, mini-Gs, at 3.4 A resolution. Mini-Gs binds to A(2A)R through an extensive interface (1,048 A2) that is similar, but not identical, to the interface between Gs and the beta2-adrenergic receptor. The transition of the receptor from an agonist-bound active-intermediate state to an active G-protein-bound state is characterized by a 14 A shift of the cytoplasmic end of transmembrane helix 6 (H6) away from the receptor core, slight changes in the positions of the cytoplasmic ends of H5 and H7 and rotamer changes of the amino acid side chains Arg3.50, Tyr5.58 and Tyr7.53. There are no substantial differences in the extracellular half of the receptor around the ligand binding pocket. The A(2A)R-mini-Gs structure highlights both the diversity and similarity in G-protein coupling to GPCRs and hints at the potential complexity of the molecular basis for G-protein specificity.
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Agonist-bound adenosine A(2A) receptor structures reveal common features of GPCR activation.,Lebon G, Warne T, Edwards PC, Bennett K, Langmead CJ, Leslie AG, Tate CG Nature. 2011 May 18. PMID:21593763<ref>PMID:21593763</ref>
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Structure of the adenosine A(2A) receptor bound to an engineered G protein.,Carpenter B, Nehme R, Warne T, Leslie AG, Tate CG Nature. 2016 Aug 4;536(7614):104-7. PMID:27462812<ref>PMID:27462812</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
<div class="pdbe-citations 5g53" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 5g53" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Adenosine A2A receptor 3D structures|Adenosine A2A receptor 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Carpenter, B]]
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[[Category: Homo sapiens]]
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[[Category: Leslie, A G.W]]
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[[Category: Large Structures]]
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[[Category: Nehme, R]]
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[[Category: Carpenter B]]
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[[Category: Tate, C G]]
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[[Category: Leslie AGW]]
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[[Category: Warne, T]]
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[[Category: Nehme R]]
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[[Category: Adenosine receptor]]
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[[Category: Tate CG]]
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[[Category: Engineered g protein]]
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[[Category: Warne T]]
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[[Category: G protein coupled receptor]]
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[[Category: Gpcr]]
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[[Category: Gpcr-g protein complex]]
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[[Category: Integral membrane protein]]
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[[Category: Mini-g]]
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[[Category: Seven-helix receptor]]
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[[Category: Signaling protein]]
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Current revision

Structure of the adenosine A2A receptor bound to an engineered G protein

PDB ID 5g53

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