Structural basis for Ca2+-dependent activation of a plant metacaspase

• Published in: Nature communications 2020-05, Vol.11 (1), p.2249-2249, Article 2249
• Main Authors: Zhu, Ping, Yu, Xiao-Hong, Wang, Cheng, Zhang, Qingfang, Liu, Wu, McSweeney, Sean, Shanklin, John, Lam, Eric, Liu, Qun
• Format: Article
• Language: English
• Subjects: 101/1; 631/449/2169; 631/45/535/1266; 82/16; 82/29; 82/47; 82/58; 82/80; 82/83; Abiotic stress; Apoptosis; BASIC BIOLOGICAL SCIENCES; Biofuels; Calcium; Calcium ions; Cell death; Conformation; Crystal structure; Crystallography; Damage; Domains; Food plants; Humanities and Social Sciences; Immune response; Immune system; Laboratories; multidisciplinary; Pathogens; Science; Science (multidisciplinary); Stresses; Substrates
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15830-8

Plant metacaspases mediate programmed cell death in development, biotic and abiotic stresses, damage-induced immune response, and resistance to pathogen attack. Most metacaspases require Ca 2+ for their activation and substrate processing. However, the Ca 2+ -dependent activation mechanism remains elusive. Here we report the crystal structures of Metacaspase 4 from Arabidopsis thaliana ( At MC4) that modulates Ca 2+ -dependent, damage-induced plant immune defense. The At MC4 structure exhibits an inhibitory conformation in which a large linker domain blocks activation and substrate access. In addition, the side chain of Lys225 in the linker domain blocks the active site by sitting directly between two catalytic residues. We show that the activation of At MC4 and cleavage of its physiological substrate involve multiple cleavages in the linker domain upon activation by Ca 2+ . Our analysis provides insight into the Ca 2+ -dependent activation of At MC4 and lays the basis for tuning its activity in response to stresses for engineering of more sustainable crops for food and biofuels. Plant metacaspases mediate immune response following activation by Ca 2+ . Here, via crystallography and functional analyses, the authors show that a linker domain in Arabidopsis Metacaspase 4 blocks substrate access to the active site but is cleaved multiple times in the presence of Ca 2+ to allow enzyme activation.