9EW2

High resolution structure of FZD7 in complex with miniGs protein

9EW2 の概要

• エントリーDOI: 10.2210/pdb9ew2/pdb
• 関連するPDBエントリー: 9EPO
• EMDBエントリー: 19881 31340
• 分子名称: GNAS complex locus,Isoform 4 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Ggamma, ... (5 entities in total)
• 機能のキーワード: gpcpr, frizzled, fzd7, 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: 159883.17

構造登録者

Bous, J.,Kinsolving, J.,Gratz, L.,Scharf, M.M.,Voss, J.,Selcuk, B.,Adebali, O.,Schulte, G. (登録日: 2024-04-03, 公開日: 2024-10-02, 最終更新日: 2025-04-09)

主引用文献

Bous, J.,Kinsolving, J.,Gratz, L.,Scharf, M.M.,Voss, J.H.,Selcuk, B.,Adebali, O.,Schulte, G.
Structural basis of frizzled 7 activation and allosteric regulation.
Nat Commun, 15:7422-7422, 2024

PubMed Abstract: Frizzleds (ten paralogs: FZD) belong to the class F of G protein-coupled receptors (GPCRs), which remains poorly understood despite its crucial role in multiple key biological functions including embryonic development, stem cell regulation, and homeostasis in the adult. FZD, one of the most studied members of the family, is more specifically involved in the migration of mesendoderm cells during the development and renewal of intestinal stem cells in adults. Moreover, FZD has been highlighted for its involvement in tumor development predominantly in the gastrointestinal tract. This study reports the structure of inactive FZD, without any stabilizing mutations, determined by cryo-electron microscopy (cryo-EM) at 1.9 Å resolution. We characterize a fluctuating water pocket in the core of the receptor important for FZD dynamics. Molecular dynamics simulations are used to investigate the temporal distribution of those water molecules and their importance for potential conformational changes in FZD. Moreover, we identify lipids interacting with the receptor core and a conserved cholesterol-binding site, which displays a key role in FZD association with a transducer protein, Disheveled (DVL), and initiation of downstream signaling and signalosome formation.

PubMed: 39198452
DOI: 10.1038/s41467-024-51664-4

実験手法

ELECTRON MICROSCOPY (3.2 Å)