+検索条件
-Structure paper
タイトル | Structures of the human cholecystokinin 1 (CCK1) receptor bound to Gs and Gq mimetic proteins provide insight into mechanisms of G protein selectivity. |
---|---|
ジャーナル・号・ページ | PLoS Biol, Vol. 19, Issue 6, Page e3001295, Year 2021 |
掲載日 | 2021年6月4日 |
著者 | Jesse I Mobbs / Matthew J Belousoff / Kaleeckal G Harikumar / Sarah J Piper / Xiaomeng Xu / Sebastian G B Furness / Hari Venugopal / Arthur Christopoulos / Radostin Danev / Denise Wootten / David M Thal / Laurence J Miller / Patrick M Sexton / |
PubMed 要旨 | 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 ...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. |
リンク | PLoS Biol / PubMed:34086670 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 1.95 - 2.44 Å |
構造データ | EMDB-23749, PDB-7mbx: EMDB-23750, PDB-7mby: |
化合物 | ChemComp-Y01: ChemComp-HOH: |
由来 |
|
キーワード | MEMBRANE PROTEIN/SIGNALING PROTEIN / GPCR / MEMBRANE PROTEIN / MEMBRANE PROTEIN-SIGNALING PROTEIN complex |