Open AccessStructural insights into differences in G protein activation by family A and family B GPCRs
Author(s) -
Daniel Hilger,
Kaavya Krishna Kumar,
Hongli Hu,
Mie Fabricius Pedersen,
Evan S. O’Brien,
Lise Giehm,
C. Jennings,
Gözde Eskici,
Asuka Inoue,
Michael T. Lerch,
Jesper Mosolff Mathiesen,
Georgios Skiniotis,
Brian K. Kobilka
Publication year - 2020
Publication title -
science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 12.556
H-Index - 1186
eISSN - 1095-9203
pISSN - 0036-8075
DOI - 10.1126/science.aba3373
Subject(s) - g protein coupled receptor , heterotrimeric g protein , g protein , gs alpha subunit , guanosine , gtpase , gtp' , chemistry , receptor , guanosine diphosphate , rhodopsin like receptors , biochemistry , biology , biophysics , agonist , guanosine triphosphate , metabotropic receptor , enzyme
Revealing family differences In response to low blood glucose concentrations, both the glucagon receptor (GCGR)—a family B G protein–coupled receptor (GPCR)—and the β2 adrenergic receptor (β2 AR)—a family A GPCR—are activated and act through the cyclic adenosine monophosphate signaling pathway to increase glucose production. The kinetics of the response is different for the two receptors. Based on structural and spectroscopic data, Hilgeret al. show that the conformation of transmembrane helix 6 in the activated state is a key differentiator (see the Perspective by Lebon). In β2 AR, the helix moves toward its active conformation when an agonist binds, but in GCGR, both agonist and G protein binding are required. This likely explains why activation of its partner G protein is slower for GCGR than for β2 AR.Science , this issue p.eaba3373 ; see also p.507
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