9UBI

Crystal structure of FERONIA kinase and Ferovicin inhibitor

9UBI の概要

• エントリーDOI: 10.2210/pdb9ubi/pdb
• 分子名称: Receptor-like protein kinase FERONIA, 1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-({trans-4-[(dimethylamino)methyl]cyclohexyl}amino)-1,5-naphthyridin-3-yl]ethanone (3 entities in total)
• 機能のキーワード: natural product biosynthetic enzyme, plant protein
• 由来する生物種: Arabidopsis thaliana (thale cress)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 74971.34

構造登録者

Sun, M.Z.,Fan, J.P.,Lei, X.G. (登録日: 2025-04-03, 公開日: 2025-10-29, 最終更新日: 2025-11-19)

主引用文献

Sun, M.,Lu, B.,Yang, Y.,Fan, J.,Ren, W.,Chu, X.,Gao, Y.,Wu, J.,Wang, J.,Ke, H.,Liu, Z.,Dai, S.,Lei, X.,Li, C.
Unveiling FERONIA receptor kinase-mediated cellular mechanisms with a small-molecule inhibitor.
Proc.Natl.Acad.Sci.USA, 122:e2515322122-e2515322122, 2025

PubMed Abstract: Since its initial identification as the receptor for Rapid Alkalinization Factor 1 (RALF1), FERONIA (FER) receptor kinase has emerged as a central signaling hub coordinating plant development, stress adaptation, and immune responses. Nevertheless, fundamental questions persist regarding the precise mechanisms of FER-mediated signal transduction and its context-dependent functional specialization in multicellular processes. Here, we develop Ferovicin (FRV), a small-molecule inhibitor that specifically disrupts FER kinase activity, thereby enabling mechanistic dissection of FER. Cocrystallization and mutational analysis show that FRV selectively binds to the ATP-binding pocket of the kinase domain of FER and inhibits its kinase activity. Assisted by the FRV tool and quantitative phosphoproteomics, we characterized a series of signaling pathways and networks regulated by RALF1 and FER. Notably, our analysis reveals that RALF1 activates FER through phosphorylation at Ser695, which subsequently inhibits H-ATPase1/2 via phosphorylation at Ser899. This mechanism leads to apoplastic alkalinization and regulates cell expansion in the root meristem. Given the conservation of FRV binding sites in FER proteins across land plant species, FRV will serve as a valuable tool for dissecting FER signaling mechanisms as well as facilitating agricultural applications.

PubMed: 41196348
DOI: 10.1073/pnas.2515322122

実験手法

X-RAY DIFFRACTION (1.9 Å)