Stael, Simon
- Department of Molecular Sciences, Swedish University of Agricultural Sciences
- Ghent University
Research article2023Peer reviewedOpen access
Structure-function study of a Ca2+-independent metacaspase involved in lateral root emergence
Stael, Simon; Sabljic, Igor; Audenaert, Dominique; Andersson , Thilde; Tsiatsiani, Liana; Kumpf, Robert P.; Vidal-Albalat, Andreu; Lindgren, Cecilia; Vercammen, Dominique; Jacques, Silke; Nguyen, Long; Njo, Maria; Fernández-Fernández, Álvaro D.; Beunens, Tine; Timmerman, Evy; Gevaert, Kris; van Montagu, Marc C. E.; Ståhlberg, Jerry; Bozhkov, Peter; Linusson, Anna;
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Abstract
Metacaspases are part of an evolutionarily broad family of multifunctional cysteine pro -teases, involved in disease and normal development. As the structure-function relation-ship of metacaspases remains poorly understood, we solved the X-ray crystal structure of an Arabidopsis thaliana type II metacaspase (AtMCA-IIf) belonging to a particular subgroup not requiring calcium ions for activation. To study metacaspase activity in plants, we developed an in vitro chemical screen to identify small molecule metacaspase inhibitors and found several hits with a minimal thioxodihydropyrimidine-dione structure, of which some are specific AtMCA-IIf inhibitors. We provide mechanistic insight into the basis of inhibition by the TDP-containing compounds through molecular docking onto the AtMCA-IIf crystal structure. Finally, a TDP-containing compound (TDP6) effectively hampered lateral root emergence in vivo, probably through inhibition of metacaspases specifically expressed in the endodermal cells overlying developing lateral root primordia. In the future, the small compound inhibitors and crystal structure of AtMCA-IIf can be used to study metacaspases in other species, such as important human pathogens, including those causing neglected diseases.
Keywords
AtMCA-IIf crystal structure; cysteine protease; lateral root development; metacaspase; small chemical inhibitor
Published in
Proceedings of the National Academy of Sciences of the United States of America
2023, volume: 120, number: 22, article number: e2303480120
SLU Authors
Sabljic, Igor
- Department of Molecular Sciences, Swedish University of Agricultural Sciences
- Department of Molecular Sciences, Swedish University of Agricultural Sciences
Ståhlberg, Jerry
- Department of Molecular Sciences, Swedish University of Agricultural Sciences
- Department of Molecular Sciences, Swedish University of Agricultural Sciences
Bozhkov, Peter
- Department of Molecular Sciences, Swedish University of Agricultural Sciences
- Department of Molecular Sciences, Swedish University of Agricultural Sciences
UKÄ Subject classification
Plant Biotechnology
Publication identifier
- DOI: https://doi.org/10.1073/pnas.2303480120
Permanent link to this page (URI)
https://res.slu.se/id/publ/123508