7WVX

Cryo-EM structure of the human formyl peptide receptor 2 in complex with fhumanin and Gi2

7WVX の概要

• エントリーDOI: 10.2210/pdb7wvx/pdb
• EMDBエントリー: 32861
• 分子名称: Humanin, Soluble cytochrome b562,N-formyl peptide receptor 2, Guanine nucleotide-binding protein G(i) subunit alpha-2, ... (5 entities in total)
• 機能のキーワード: g protein-coupled receptor, formyl peptide receptor, fpr2, humanin, signaling 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: 146537.98

構造登録者

Zhu, Y.,Lin, X.,Zong, X.,Han, S.,Zhao, Q.,Wu, B. (登録日: 2022-02-11, 公開日: 2022-04-13, 最終更新日: 2024-11-20)

主引用文献

Zhu, Y.,Lin, X.,Zong, X.,Han, S.,Wang, M.,Su, Y.,Ma, L.,Chu, X.,Yi, C.,Zhao, Q.,Wu, B.
Structural basis of FPR2 in recognition of A beta 42 and neuroprotection by humanin.
Nat Commun, 13:1775-1775, 2022

PubMed Abstract: Formyl peptide receptor 2 (FPR2) has been shown to mediate the cytotoxic effects of the β amyloid peptide Aβ and serves as a receptor for humanin, a peptide that protects neuronal cells from damage by Aβ, implying its involvement in the pathogenesis of Alzheimer's disease (AD). However, the interaction pattern between FPR2 and Aβ or humanin remains unknown. Here we report the structures of FPR2 bound to G and Aβ or N-formyl humanin (fHN). Combined with functional data, the structures reveal two critical regions that govern recognition and activity of Aβ and fHN, including a polar binding cavity within the receptor helical bundle and a hydrophobic binding groove in the extracellular region. In addition, the structures of FPR2 and FPR1 in complex with different formyl peptides were determined, providing insights into ligand recognition and selectivity of the FPR family. These findings uncover key factors that define the functionality of FPR2 in AD and other inflammatory diseases and would enable drug development.

PubMed: 35365641
DOI: 10.1038/s41467-022-29361-x

実験手法

ELECTRON MICROSCOPY (2.8 Å)