8IEC

Cryo-EM structure of miniGo-scFv16 of GPR156-miniGo-scFv16 complex (local refine)

8IEC の概要

• エントリーDOI: 10.2210/pdb8iec/pdb
• EMDBエントリー: 35378
• 分子名称: Guanine nucleotide-binding protein G(o) subunit alpha, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Single-chain variable fragment scFv16, ... (4 entities in total)
• 機能のキーワード: membrane protein, g-protein coupled receptor, signal transduction, phospholipid, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 100683.46

構造登録者

Shin, J.,Park, J.,Cho, Y. (登録日: 2023-02-15, 公開日: 2024-02-14, 最終更新日: 2024-10-30)

主引用文献

Shin, J.,Park, J.,Jeong, J.,Lam, J.H.,Qiu, X.,Wu, D.,Kim, K.,Lee, J.Y.,Robinson, C.V.,Hyun, J.,Katritch, V.,Kim, K.P.,Cho, Y.
Constitutive activation mechanism of a class C GPCR.
Nat.Struct.Mol.Biol., 31:678-687, 2024

PubMed Abstract: Class C G-protein-coupled receptors (GPCRs) are activated through binding of agonists to the large extracellular domain (ECD) followed by rearrangement of the transmembrane domains (TMDs). GPR156, a class C orphan GPCR, is unique because it lacks an ECD and exhibits constitutive activity. Impaired GPR156-G signaling contributes to loss of hearing. Here we present the cryo-electron microscopy structures of human GPR156 in the G-free and G-coupled states. We found that an endogenous phospholipid molecule is located within each TMD of the GPR156 dimer. Asymmetric binding of Gα to the phospholipid-bound GPR156 dimer restructures the first and second intracellular loops and the carboxy-terminal part of the elongated transmembrane 7 (TM7) without altering dimer conformation. Our findings reveal that GPR156 is a transducer for phospholipid signaling. Constant binding of abundant phospholipid molecules and the G-protein-induced reshaping of the cytoplasmic face provide a basis for the constitutive activation of GPR156.

PubMed: 38332368
DOI: 10.1038/s41594-024-01224-7

実験手法

ELECTRON MICROSCOPY (3.18 Å)