Stael, Simon
- Institutionen för molekylära vetenskaper, Sveriges lantbruksuniversitet
- Universiteit Gent
Forskningsartikel2023Vetenskapligt granskadÖppen tillgång
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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Sammanfattning
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.
Nyckelord
AtMCA-IIf crystal structure; cysteine protease; lateral root development; metacaspase; small chemical inhibitor
Publicerad i
Proceedings of the National Academy of Sciences of the United States of America
2023, volym: 120, nummer: 22, artikelnummer: e2303480120
SLU författare
Sabljic, Igor
- Institutionen för molekylära vetenskaper, Sveriges lantbruksuniversitet
- Institutionen för molekylära vetenskaper, Sveriges lantbruksuniversitet
Ståhlberg, Jerry
- Institutionen för molekylära vetenskaper, Sveriges lantbruksuniversitet
- Institutionen för molekylära vetenskaper, Sveriges lantbruksuniversitet
Bozhkov, Peter
- Institutionen för molekylära vetenskaper, Sveriges lantbruksuniversitet
- Institutionen för molekylära vetenskaper, Sveriges lantbruksuniversitet
UKÄ forskningsämne
Växtbioteknologi
Publikationens identifierare
- DOI: https://doi.org/10.1073/pnas.2303480120
Permanent länk till denna sida (URI)
https://res.slu.se/id/publ/123508