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5g53

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Revision as of 06:39, 13 May 2020

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

Structural highlights

5g53 is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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

[AA2AR_HUMAN] Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. [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).^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

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.

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^[6]

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

References

↑ Pak Y, Pham N, Rotin D. Direct binding of the beta1 adrenergic receptor to the cyclic AMP-dependent guanine nucleotide exchange factor CNrasGEF leads to Ras activation. Mol Cell Biol. 2002 Nov;22(22):7942-52. PMID:12391161
↑ Gao X, Sadana R, Dessauer CW, Patel TB. Conditional stimulation of type V and VI adenylyl cyclases by G protein betagamma subunits. J Biol Chem. 2007 Jan 5;282(1):294-302. Epub 2006 Nov 16. PMID:17110384 doi:http://dx.doi.org/10.1074/jbc.M607522200
↑ Thiele S, de Sanctis L, Werner R, Grotzinger J, Aydin C, Juppner H, Bastepe M, Hiort O. Functional characterization of GNAS mutations found in patients with pseudohypoparathyroidism type Ic defines a new subgroup of pseudohypoparathyroidism affecting selectively Gsalpha-receptor interaction. Hum Mutat. 2011 Jun;32(6):653-60. doi: 10.1002/humu.21489. Epub 2011 Apr 12. PMID:21488135 doi:http://dx.doi.org/10.1002/humu.21489
↑ Brand CS, Sadana R, Malik S, Smrcka AV, Dessauer CW. Adenylyl Cyclase 5 Regulation by Gbetagamma Involves Isoform-Specific Use of Multiple Interaction Sites. Mol Pharmacol. 2015 Oct;88(4):758-67. doi: 10.1124/mol.115.099556. Epub 2015 Jul , 23. PMID:26206488 doi:http://dx.doi.org/10.1124/mol.115.099556
↑ Farfel Z, Iiri T, Shapira H, Roitman A, Mouallem M, Bourne HR. Pseudohypoparathyroidism, a novel mutation in the betagamma-contact region of Gsalpha impairs receptor stimulation. J Biol Chem. 1996 Aug 16;271(33):19653-5. PMID:8702665
↑ Carpenter B, Nehme R, Warne T, Leslie AG, Tate CG. Structure of the adenosine A(2A) receptor bound to an engineered G protein. Nature. 2016 Aug 4;536(7614):104-7. PMID:27462812 doi:http://dx.doi.org/10.1038/nature18966

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5g53"

@@ Line 1: / Line 1: @@
 ==Structure of the adenosine A2A receptor bound to an engineered G protein==
-<StructureSection load='5g53' size='340' side='right' caption='[[5g53]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
+<StructureSection load='5g53' size='340' side='right'caption='[[5g53]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
 == Structural highlights ==
-<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>
+<table><tr><td colspan='2'>[[5g53]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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://proteopedia.org/fgij/fg.htm?mol=5G53 FirstGlance]. <br>
-</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>
+</td></tr><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>
-<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>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/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>
 </table>
 == Disease ==
@@ Line 22: / Line 22: @@
 ==See Also==
-*[[Adenosine A2A receptor|Adenosine A2A receptor]]
+*[[Adenosine A2A receptor 3D structures|Adenosine A2A receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Carpenter, B]]
 [[Category: Leslie, A G.W]]

5g53

From Proteopedia

Revision as of 06:39, 13 May 2020

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

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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