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| | <SX load='5vai' size='340' side='right' viewer='molstar' caption='[[5vai]], [[Resolution|resolution]] 4.10Å' scene=''> | | <SX load='5vai' size='340' side='right' viewer='molstar' caption='[[5vai]], [[Resolution|resolution]] 4.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5vai]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Bovin Bovin], [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat], [http://en.wikipedia.org/wiki/Camelus_glama Camelus glama], [http://en.wikipedia.org/wiki/European_rabbit European rabbit] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VAI OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5VAI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5vai]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Lama_glama Lama glama], [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VAI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VAI FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GLP1R ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 European rabbit]), GNAS, GNAS1, GSP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Gnb1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat]), GNG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9913 BOVIN])</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]] 4.1Å</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=5vai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vai OCA], [http://pdbe.org/5vai PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vai RCSB], [http://www.ebi.ac.uk/pdbsum/5vai PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vai 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=5vai FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vai OCA], [https://pdbe.org/5vai PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vai RCSB], [https://www.ebi.ac.uk/pdbsum/5vai PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vai ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | == Disease == | |
| - | [[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 == |
| - | [[http://www.uniprot.org/uniprot/GBB1_RAT GBB1_RAT]] 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. [[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> [[http://www.uniprot.org/uniprot/GLUC_HUMAN GLUC_HUMAN]] Glucagon plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes.<ref>PMID:8482423</ref> <ref>PMID:14557443</ref> <ref>PMID:14632334</ref> GLP-1 is a potent stimulator of glucose-dependent insulin release. Play important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Have growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation. Inhibits beta cell apoptosis.<ref>PMID:8482423</ref> <ref>PMID:14557443</ref> <ref>PMID:14632334</ref> GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability.<ref>PMID:8482423</ref> <ref>PMID:14557443</ref> <ref>PMID:14632334</ref> Oxyntomodulin significantly reduces food intake. Inhibits gastric emptying in humans. Suppression of gastric emptying may lead to increased gastric distension, which may contribute to satiety by causing a sensation of fullness.<ref>PMID:8482423</ref> <ref>PMID:14557443</ref> <ref>PMID:14632334</ref> Glicentin may modulate gastric acid secretion and the gastro-pyloro-duodenal activity. May play an important role in intestinal mucosal growth in the early period of life.<ref>PMID:8482423</ref> <ref>PMID:14557443</ref> <ref>PMID:14632334</ref> [[http://www.uniprot.org/uniprot/GBG2_BOVIN GBG2_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. | + | [https://www.uniprot.org/uniprot/G1SGD4_RABIT G1SGD4_RABIT] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| | + | *[[Glucagon-like peptide receptor 3D structures|Glucagon-like peptide receptor 3D structures]] |
| | *[[Transducin 3D structures|Transducin 3D structures]] | | *[[Transducin 3D structures|Transducin 3D structures]] |
| | == References == | | == References == |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Bovin]] | + | [[Category: Bos taurus]] |
| - | [[Category: Buffalo rat]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Camelus glama]] | + | [[Category: Lama glama]] |
| - | [[Category: European rabbit]]
| + | |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chu, M]] | + | [[Category: Oryctolagus cuniculus]] |
| - | [[Category: Feng, D]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Hu, H]] | + | [[Category: Chu M]] |
| - | [[Category: Kobilka, B K]] | + | [[Category: Feng D]] |
| - | [[Category: Kobilka, T S]] | + | [[Category: Hu H]] |
| - | [[Category: Li, S]] | + | [[Category: Kobilka BK]] |
| - | [[Category: Qu, Q]] | + | [[Category: Kobilka TS]] |
| - | [[Category: Skiniotis, G]] | + | [[Category: Li S]] |
| - | [[Category: Sun, B]] | + | [[Category: Qu Q]] |
| - | [[Category: Tarrasch, J T]] | + | [[Category: Skiniotis G]] |
| - | [[Category: Zhang, Y]] | + | [[Category: Sun B]] |
| - | [[Category: Class b gpcr]]
| + | [[Category: Tarrasch JT]] |
| - | [[Category: Complex]]
| + | [[Category: Zhang Y]] |
| - | [[Category: Glp-1]]
| + | |
| - | [[Category: Glp-1r]]
| + | |
| - | [[Category: Signaling protein-hormone complex]]
| + | |
| Structural highlights
Function
G1SGD4_RABIT
Publication Abstract from PubMed
Glucagon-like peptide 1 (GLP-1) is a hormone with essential roles in regulating insulin secretion, carbohydrate metabolism and appetite. GLP-1 effects are mediated through binding to the GLP-1 receptor (GLP-1R), a class B G-protein-coupled receptor (GPCR) that signals primarily through the stimulatory G protein Gs. Class B GPCRs are important therapeutic targets; however, our understanding of their mechanism of action is limited by the lack of structural information on activated and full-length receptors. Here we report the cryo-electron microscopy structure of the peptide-activated GLP-1R-Gs complex at near atomic resolution. The peptide is clasped between the N-terminal domain and the transmembrane core of the receptor, and further stabilized by extracellular loops. Conformational changes in the transmembrane domain result in a sharp kink in the middle of transmembrane helix 6, which pivots its intracellular half outward to accommodate the alpha5-helix of the Ras-like domain of Gs. These results provide a structural framework for understanding class B GPCR activation through hormone binding.
Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein.,Zhang Y, Sun B, Feng D, Hu H, Chu M, Qu Q, Tarrasch JT, Li S, Sun Kobilka T, Kobilka BK, Skiniotis G Nature. 2017 Jun 8;546(7657):248-253. doi: 10.1038/nature22394. Epub 2017 May 24. PMID:28538729[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang Y, Sun B, Feng D, Hu H, Chu M, Qu Q, Tarrasch JT, Li S, Sun Kobilka T, Kobilka BK, Skiniotis G. Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein. Nature. 2017 Jun 8;546(7657):248-253. doi: 10.1038/nature22394. Epub 2017 May 24. PMID:28538729 doi:http://dx.doi.org/10.1038/nature22394
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