7QBC

Structure of the GPCR dimer Ste2 in the inactive-like state bound to agonist

7QBC の概要

• エントリーDOI: 10.2210/pdb7qbc/pdb
• 関連するPDBエントリー: 7QA8 7QB9
• EMDBエントリー: 13880 13882 13886
• 分子名称: Pheromone alpha factor receptor, Alpha factor pheromone, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: gpcr, dimer, antagonist-bound, fungal, membrane protein
• 由来する生物種: Saccharomyces cerevisiae (Baker's yeast); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 105868.32

構造登録者

Velazhahan, V.,Tate, C.G. (登録日: 2021-11-18, 公開日: 2022-03-16, 最終更新日: 2022-04-06)

主引用文献

Velazhahan, V.,Ma, N.,Vaidehi, N.,Tate, C.G.
Activation mechanism of the class D fungal GPCR dimer Ste2.
Nature, 603:743-748, 2022

PubMed Abstract: The fungal class D1 G-protein-coupled receptor (GPCR) Ste2 has a different arrangement of transmembrane helices compared with mammalian GPCRs and a distinct mode of coupling to the heterotrimeric G protein Gpa1-Ste2-Ste18. In addition, Ste2 lacks conserved sequence motifs such as DRY, PIF and NPXXY, which are associated with the activation of class A GPCRs. This suggested that the activation mechanism of Ste2 may also differ. Here we determined structures of Saccharomyces cerevisiae Ste2 in the absence of G protein in two different conformations bound to the native agonist α-factor, bound to an antagonist and without ligand. These structures revealed that Ste2 is indeed activated differently from other GPCRs. In the inactive state, the cytoplasmic end of transmembrane helix H7 is unstructured and packs between helices H1-H6, blocking the G protein coupling site. Agonist binding results in the outward movement of the extracellular ends of H6 and H7 by 6 Å. On the intracellular surface, the G protein coupling site is formed by a 20 Å outward movement of the unstructured region in H7 that unblocks the site, and a 12 Å inward movement of H6. This is a distinct mechanism in GPCRs, in which the movement of H6 and H7 upon agonist binding facilitates G protein coupling.

PubMed: 35296853
DOI: 10.1038/s41586-022-04498-3

実験手法

ELECTRON MICROSCOPY (3.53 Å)