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TitleStructural basis of G and G recognition by the human glucagon receptor.
Journal, issue, pagesScience, Vol. 367, Issue 6484, Page 1346-1352, Year 2020
Publish dateMar 20, 2020
AuthorsAnna Qiao / Shuo Han / Xinmei Li / Zhixin Li / Peishen Zhao / Antao Dai / Rulve Chang / Linhua Tai / Qiuxiang Tan / Xiaojing Chu / Limin Ma / Thor Seneca Thorsen / Steffen Reedtz-Runge / Dehua Yang / Ming-Wei Wang / Patrick M Sexton / Denise Wootten / Fei Sun / Qiang Zhao / Beili Wu /
PubMed AbstractClass B G protein-coupled receptors, an important class of therapeutic targets, signal mainly through the G class of heterotrimeric G proteins, although they do display some promiscuity in G protein ...Class B G protein-coupled receptors, an important class of therapeutic targets, signal mainly through the G 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, G or G These two structures adopt a similar open binding cavity to accommodate G and G The G binding selectivity of GCGR is explained by a larger interaction interface, but there are specific interactions that affect G more than G 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.
External linksScience / PubMed:32193322
MethodsEM (single particle)
Resolution3.7 - 3.9 Å
Structure data

0917

6lmk

EMDB-0917, PDB-6lmk:
Cryo-EM structure of the human glucagon receptor in complex with Gs
Method: EM (single particle) / Resolution: 3.7 Å

0918

6lml

EMDB-0918, PDB-6lml:
Cryo-EM structure of the human glucagon receptor in complex with Gi1
Method: EM (single particle) / Resolution: 3.9 Å

Source
  • homo sapiens (human)
  • lama glama (llama)
  • mus musculus (house mouse)
KeywordsSIGNALING PROTEIN / glucagon receptor / GPCR / Gs protein / Gi1 protein

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