In:
PLOS Biology, Public Library of Science (PLoS), Vol. 19, No. 6 ( 2021-6-4), p. e3001295-
Abstract:
G protein–coupled receptors (GPCRs) are critical regulators of cellular function acting via heterotrimeric G proteins as their primary transducers with individual GPCRs capable of pleiotropic coupling to multiple G proteins. Structural features governing G protein selectivity and promiscuity are currently unclear. Here, we used cryo-electron microscopy (cryo-EM) to determine structures of the cholecystokinin (CCK) type 1 receptor (CCK1R) bound to the CCK peptide agonist, CCK-8 and 2 distinct transducer proteins, its primary transducer Gq, and the more weakly coupled Gs. As seen with other Gq/11–GPCR complexes, the Gq–α5 helix (αH5) bound to a relatively narrow pocket in the CCK1R core. Surprisingly, the backbone of the CCK1R and volume of the G protein binding pocket were essentially equivalent when Gs was bound, with the Gs αH5 displaying a conformation that arises from “unwinding” of the far carboxyl-terminal residues, compared to canonically Gs coupled receptors. Thus, integrated changes in the conformations of both the receptor and G protein are likely to play critical roles in the promiscuous coupling of individual GPCRs.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001295
DOI:
10.1371/journal.pbio.3001295.g001
DOI:
10.1371/journal.pbio.3001295.g002
DOI:
10.1371/journal.pbio.3001295.g003
DOI:
10.1371/journal.pbio.3001295.g004
DOI:
10.1371/journal.pbio.3001295.t001
DOI:
10.1371/journal.pbio.3001295.t002
DOI:
10.1371/journal.pbio.3001295.s001
DOI:
10.1371/journal.pbio.3001295.s002
DOI:
10.1371/journal.pbio.3001295.s003
DOI:
10.1371/journal.pbio.3001295.s004
DOI:
10.1371/journal.pbio.3001295.s005
DOI:
10.1371/journal.pbio.3001295.s006
DOI:
10.1371/journal.pbio.3001295.s007
DOI:
10.1371/journal.pbio.3001295.s008
DOI:
10.1371/journal.pbio.3001295.s009
DOI:
10.1371/journal.pbio.3001295.s010
DOI:
10.1371/journal.pbio.3001295.s011
DOI:
10.1371/journal.pbio.3001295.s012
DOI:
10.1371/journal.pbio.3001295.s013
DOI:
10.1371/journal.pbio.3001295.s014
DOI:
10.1371/journal.pbio.3001295.s015
DOI:
10.1371/journal.pbio.3001295.s016
DOI:
10.1371/journal.pbio.3001295.s017
DOI:
10.1371/journal.pbio.3001295.s018
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2126773-X
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