9nsi: Difference between revisions

Latest revision as of 09:23, 30 September 2026

Cryo-EM structure of GLP-1R-Gs complex with GLP-1 (9-36) and cpd19

Structural highlights

9nsi is a 6 chain structure with sequence from Homo sapiens, Lama glama and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.2Å
Ligands:	A1B0V
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

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]

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:https://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:https://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:https://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

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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:https://dx.doi.org/10.1074/jbc.M607522200

[3] 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:https://dx.doi.org/10.1002/humu.21489

[4] 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:https://dx.doi.org/10.1124/mol.115.099556

[5] 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

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[2]

[3]

[4]

[5]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9nsi is ON HOLD  until Paper Publication
+==Cryo-EM structure of GLP-1R-Gs complex with GLP-1 (9-36) and cpd19==
+<StructureSection load='9nsi' size='340' side='right'caption='[[9nsi]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
-Authors: Zhang, X., Belousoff, M.J., Wootten, D., Patrick, P.M.
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9nsi]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Lama_glama Lama glama] 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=9NSI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9NSI FirstGlance]. <br>
-Description: Cryo-EM structure of GLP-1R-Gs complex with GLP-1 (9-36) and cpd19
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
-[[Category: Unreleased Structures]]
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1B0V:{(2S,4S,6R,13R,13aS)-12-(tert-butoxycarbonyl)-14-[(4,4-difluorocyclohexyl)acetyl]-5-oxo-2,3,5,6,7,12,13,13a-octahydro-1H-6,13-epiminopyrrolo[1,2 1,2]azocino[4,5-b]indol-2-yl}acetic+acid'>A1B0V</scene></td></tr>
-[[Category: Wootten, D]]
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9nsi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9nsi OCA], [https://pdbe.org/9nsi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9nsi RCSB], [https://www.ebi.ac.uk/pdbsum/9nsi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9nsi ProSAT]</span></td></tr>
-[[Category: Patrick, P.M]]
+</table>
-[[Category: Zhang, X]]
+== Disease ==
-[[Category: Belousoff, M.J]]
+[https://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 ==
+[https://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>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Lama glama]]
+[[Category: Large Structures]]
+[[Category: Synthetic construct]]
+[[Category: Belousoff MJ]]
+[[Category: Patrick PM]]
+[[Category: Wootten D]]
+[[Category: Zhang X]]

9nsi: Difference between revisions

Latest revision as of 09:23, 30 September 2026

Cryo-EM structure of GLP-1R-Gs complex with GLP-1 (9-36) and cpd19

Structural highlights

Disease

Function

References

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