9K20
Cryo-EM structure of ATP-bound P2Y purinoceptor 2-miniGo-scFv16 complex
9K20 の概要
エントリーDOI | 10.2210/pdb9k20/pdb |
EMDBエントリー | 61986 |
分子名称 | P2Y purinoceptor 2, Guanine nucleotide-binding protein G(o) subunit alpha, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (6 entities in total) |
機能のキーワード | g protein-coupled receptors, g-protein signaling, nucleotide receptors, membrane protein |
由来する生物種 | Homo sapiens (human) 詳細 |
タンパク質・核酸の鎖数 | 5 |
化学式量合計 | 150873.33 |
構造登録者 | |
主引用文献 | Lan, B.,Zhang, S.,Chen, K.,Dai, S.,Fei, J.,Gao, K.,Sun, X.,Lin, B.,Liu, X. Structural insight into the self-activation and G-protein coupling of P2Y2 receptor. Cell Discov, 11:47-47, 2025 Cited by PubMed Abstract: Purinergic P2Y2 receptor (P2Y2R) represents a typically extracellular ATP and UTP sensor for mediating purinergic signaling. Despite its importance as a pharmacological target, the molecular mechanisms underlying ligand recognition and G-protein coupling have remained elusive due to lack of structural information. In this study, we determined the cryo-electron microscopy (cryo-EM) structures of the apo P2Y2R in complex with G, ATP-bound P2Y2R in complex with G or G, and UTP-bound P2Y4R in complex with G. These structures reveal the similarities and distinctions of ligand recognition within the P2Y receptor family. Furthermore, a comprehensive analysis of G-protein coupling reveals that P2Y2R exhibits promiscuity in coupling with both G and G proteins. Combining molecular dynamics simulations and signaling assays, we elucidate the molecular mechanisms by which P2Y2R differentiates pathway-specific G or G coupling through distinct structural components on the intracellular side. Strikingly, we identify a helix-like segment within the N-terminus that occupies the orthosteric ligand-binding pocket of P2Y2R, accounting for its self-activation. Taken together, these findings provide a molecular framework for understanding the activation mechanism of P2Y2R, encompassing ligand recognition, G-protein coupling, and a novel N-terminus-mediated self-activation mechanism. PubMed: 40360475DOI: 10.1038/s41421-025-00797-x 主引用文献が同じPDBエントリー |
実験手法 | ELECTRON MICROSCOPY (2.65 Å) |
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