Screening and identification of a non-peptide antagonist for the peptide hormone receptor in Arabidopsis

Communications Biology
Hidefumi ShinoharaYoshikatsu Matsubayashi

Abstract

Intercellular signaling mediated by peptide hormones and membrane-localized receptor kinases plays crucial roles in plant developmental processes. Because of their diverse functions, agonistic or antagonistic modulation of peptide signaling holds enormous promise for agricultural applications. Here we established a high-throughput screening system using a bead-immobilized receptor kinase and fluorescent-labeled peptide ligand to identify small molecules that bind peptide hormone receptors in competition with natural ligands. We used the Arabidopsis CLE9-BAM1 ligand-receptor pair to screen a library of ≈30,000 chemicals and identified NPD12704 as an antagonist for BAM1. NPD12704 also inhibited CLV3 binding to BAM1 but only minimally interfered with CLV3 binding to CLV1, the closest homolog of BAM1, demonstrating preferential receptor specificity. Treatment of clv1-101 mutant seedlings with NPD12704 enhanced the enlarged shoot apical meristem phenotype. Our results provide a technological framework enabling high-throughput identification of small non-peptide chemicals that specifically control receptor kinase-mediated peptide hormone signaling in plants.

References

Dec 22, 2005·The Plant Journal : for Cell and Molecular Biology·Brody J DeYoungSteven E Clark
Jul 31, 2007·The Plant Journal : for Cell and Molecular Biology·Hidefumi Shinohara, Yoshikatsu Matsubayashi
Jan 19, 2008·Science·Mari OgawaYoshikatsu Matsubayashi
Jun 16, 2009·Nature Chemical Biology·Kentaro OhyamaYoshikatsu Matsubayashi
Feb 15, 2011·Journal of Experimental Botany·Eleanor MarshallJose Gutierrez-Marcos
Feb 11, 2012·The Plant Journal : for Cell and Molecular Biology·Hidefumi ShinoharaYoshikatsu Matsubayashi
Mar 13, 2012·Current Opinion in Chemical Biology·Naoki KatoHiroyuki Osada
May 2, 2014·Annual Review of Plant Biology·Yoshikatsu Matsubayashi
Jul 19, 2014·Nature Reviews. Drug Discovery·Jörg EderChristian Wiesmann
Aug 16, 2014·Frontiers in Plant Science·Adeline RigalStéphanie Robert
Dec 3, 2014·Current Opinion in Plant Biology·Etienne Grienenberger, Jennifer C Fletcher
Mar 11, 2015·The Plant Journal : for Cell and Molecular Biology·Hidefumi Shinohara, Yoshikatsu Matsubayashi
Aug 9, 2016·Nature Communications·Junko MoritaOsamu Nureki
Oct 28, 2017·Nature Reviews. Drug Discovery·Alexander S HauserDavid E Gloriam
Dec 14, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Feng-Ling TukunJo Klaveness
Jan 26, 2018·Trends in Plant Science·Eunkyoo OhJungmook Kim

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Citations

Oct 23, 2019·Nature Chemical Biology·Vivek Halder, Eugenia Russinova

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Methods Mentioned

BETA
PCR

Software Mentioned

Columbus
Opera
ImageJ
iLinkPro
NPDepo

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