View source for 6lmk


==Cryo-EM structure of the human glucagon receptor in complex with Gs==
<StructureSection load='6lmk' size='340' side='right'caption='[[6lmk]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6lmk]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LMK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LMK 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]] 3.7&#8491;</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=6lmk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6lmk OCA], [https://pdbe.org/6lmk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6lmk RCSB], [https://www.ebi.ac.uk/pdbsum/6lmk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6lmk ProSAT]</span></td></tr>
</table>
== Function ==
[https://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> 
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== Publication Abstract from PubMed ==
Class B G protein-coupled receptors, an important class of therapeutic targets, signal mainly through the Gs class of heterotrimeric G proteins, although they do display some promiscuity in G protein binding. Using cryo-electron microscopy, we determined the structures of the human glucagon receptor (GCGR) bound to glucagon and distinct classes of heterotrimeric G proteins, Gs or Gi1 These two structures adopt a similar open binding cavity to accommodate Gs and Gi1 The Gs binding selectivity of GCGR is explained by a larger interaction interface, but there are specific interactions that affect Gi more than Gs binding. Conformational differences in the receptor intracellular loops were found to be key selectivity determinants. These distinctions in transducer engagement were supported by mutagenesis and functional studies.

Structural basis of Gs and Gi recognition by the human glucagon receptor.,Qiao A, Han S, Li X, Li Z, Zhao P, Dai A, Chang R, Tai L, Tan Q, Chu X, Ma L, Thorsen TS, Reedtz-Runge S, Yang D, Wang MW, Sexton PM, Wootten D, Sun F, Zhao Q, Wu B Science. 2020 Mar 20;367(6484):1346-1352. doi: 10.1126/science.aaz5346. PMID:32193322<ref>PMID:32193322</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 6lmk" style="background-color:#fffaf0;"></div>

==See Also==
*[[GTP-binding protein 3D structures|GTP-binding protein 3D structures]]
*[[Glucagon receptor|Glucagon receptor]]
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Han S]]
[[Category: Qiao A]]
[[Category: Sun F]]
[[Category: Tai L]]
[[Category: Wu B]]
[[Category: Zhao Q]]