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The | ==Cryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and coupled with heterotrimeric G11 protein== | ||
<StructureSection load='7try' size='340' side='right'caption='[[7try]], [[Resolution|resolution]] 3.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7try]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] 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=7TRY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TRY 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]] 3.7Å</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=7try FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7try OCA], [https://pdbe.org/7try PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7try RCSB], [https://www.ebi.ac.uk/pdbsum/7try PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7try ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CRFR2_HUMAN CRFR2_HUMAN] G-protein coupled receptor for CRH (corticotropin-releasing factor), UCN (urocortin), UCN2 and UCN3. Has high affinity for UCN. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and down-stream effectors, such as adenylate cyclase. Promotes the activation of adenylate cyclase, leading to increased intracellular cAMP levels. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The ability to couple with multiple G protein subtypes, such as G(s), G(i/o), or G(q/11), by a given G protein-coupled receptor (GPCR) is critical for many physiological processes. Over the past few years, the cryo-EM structures for all 15 members of the medically important class B GPCRs, all in complex with G(s) protein, have been determined. However, no structure of class B GPCRs with G(q/11) has been solved to date, limiting our understanding of the precise mechanisms of G protein coupling selectivity. Here we report the structures of corticotropin releasing factor receptor 2 (CRF2R) bound to Urocortin 1 (UCN1), coupled with different classes of heterotrimeric G proteins, G(11) and G(o). We compare these structures with the structure of CRF2R in complex with G(s) to uncover the structural differences that determine the selective coupling of G protein subtypes by CRF2R. These results provide important insights into the structural basis for the ability of CRF2R to couple with multiple G protein subtypes. | |||
Structure insights into selective coupling of G protein subtypes by a class B G protein-coupled receptor.,Zhao LH, Lin J, Ji SY, Zhou XE, Mao C, Shen DD, He X, Xiao P, Sun J, Melcher K, Zhang Y, Yu X, Xu HE Nat Commun. 2022 Nov 5;13(1):6670. doi: 10.1038/s41467-022-33851-3. PMID:36335102<ref>PMID:36335102</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7try" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Transducin 3D structures|Transducin 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: Melcher | __TOC__ | ||
[[Category: Xiao | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Rattus norvegicus]] | ||
[[Category: Synthetic construct]] | |||
[[Category: Ji S]] | |||
[[Category: Lin J]] | |||
[[Category: Mao C]] | |||
[[Category: Melcher K]] | |||
[[Category: Shen D]] | |||
[[Category: Xiao P]] | |||
[[Category: Xu HE]] | |||
[[Category: Yu X]] | |||
[[Category: Zhang Y]] | |||
[[Category: Zhao L-H]] | |||
[[Category: Zhou XE]] | |||
Latest revision as of 17:04, 6 November 2024
Cryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and coupled with heterotrimeric G11 proteinCryo-EM structure of corticotropin releasing factor receptor 2 bound to Urocortin 1 and coupled with heterotrimeric G11 protein
Structural highlights
FunctionCRFR2_HUMAN G-protein coupled receptor for CRH (corticotropin-releasing factor), UCN (urocortin), UCN2 and UCN3. Has high affinity for UCN. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and down-stream effectors, such as adenylate cyclase. Promotes the activation of adenylate cyclase, leading to increased intracellular cAMP levels. Publication Abstract from PubMedThe ability to couple with multiple G protein subtypes, such as G(s), G(i/o), or G(q/11), by a given G protein-coupled receptor (GPCR) is critical for many physiological processes. Over the past few years, the cryo-EM structures for all 15 members of the medically important class B GPCRs, all in complex with G(s) protein, have been determined. However, no structure of class B GPCRs with G(q/11) has been solved to date, limiting our understanding of the precise mechanisms of G protein coupling selectivity. Here we report the structures of corticotropin releasing factor receptor 2 (CRF2R) bound to Urocortin 1 (UCN1), coupled with different classes of heterotrimeric G proteins, G(11) and G(o). We compare these structures with the structure of CRF2R in complex with G(s) to uncover the structural differences that determine the selective coupling of G protein subtypes by CRF2R. These results provide important insights into the structural basis for the ability of CRF2R to couple with multiple G protein subtypes. Structure insights into selective coupling of G protein subtypes by a class B G protein-coupled receptor.,Zhao LH, Lin J, Ji SY, Zhou XE, Mao C, Shen DD, He X, Xiao P, Sun J, Melcher K, Zhang Y, Yu X, Xu HE Nat Commun. 2022 Nov 5;13(1):6670. doi: 10.1038/s41467-022-33851-3. PMID:36335102[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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