7MBY

Human Cholecystokinin 1 receptor (CCK1R) Gq chimera (mGsqi) complex

Summary for 7MBY

• Entry DOI: 10.2210/pdb7mby/pdb
• EMDB information: 23750
• Descriptor: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, Cholecystokinin-8, ... (6 entities in total)
• Functional Keywords: gpcr, membrane protein, membrane protein-signaling protein complex, membrane protein/signaling protein
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 5
• Total formula weight: 123806.90

Authors

Mobbs, J.I.,Belousoff, M.J.,Danev, R.,Thal, D.M.,Sexton, P.M. (deposition date: 2021-04-01, release date: 2021-05-26, Last modification date: 2025-05-14)

Primary citation

Mobbs, J.I.,Belousoff, M.J.,Harikumar, K.G.,Piper, S.J.,Xu, X.,Furness, S.G.B.,Venugopal, H.,Christopoulos, A.,Danev, R.,Wootten, D.,Thal, D.M.,Miller, L.J.,Sexton, P.M.
Structures of the human cholecystokinin 1 (CCK1) receptor bound to Gs and Gq mimetic proteins provide insight into mechanisms of G protein selectivity.
Plos Biol., 19:e3001295-e3001295, 2021

PubMed 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.

PubMed: 34086670
DOI: 10.1371/journal.pbio.3001295

Experimental method

ELECTRON MICROSCOPY (2.44 Å)