Caspase activation mechanism

Caspase activation is a sequential multi-step hydrolysis process. Caspase molecules are different, but their activation processes are similar. First, the N-terminal prepeptide is hydrolyzed to remove the N-terminal prepeptide at a specific site between the N-terminal prepeptide and the large subunit of the caspase precursor, and then the large and small subunits are cut and released. The heterodimer is composed of the large subunit and the small subunit, and then the two dimers form an active tetramer. Removal of N-terminal prepreptide is the first step in the activation of Caspase, and it is also necessary. However, the activation of Caspase-9 does not require removal of N-terminal prepreptide. There are basically two mechanisms for Caspase activation, namely homologous activation and heterogeneous activation. These two activation methods are closely related. Generally speaking, the latter is the result of the former. Caspase that undergoes homologous activation is also called initiator caspase, including caspase-8, - 10, - 9. After inducing apoptosis, The initial caspase is recruited to a specific initial activation complex through the adapter, forming a homodimer structure change, leading to the enzymatic digestion between homologous molecules and self activation. Generally, caspase-8, 10, and 2 mediate the apoptosis of cells in the death receptor pathway, and are recruited to the Fas and TNFR1 death receptor complexes respectively, while caspase-9 participates in the apoptosis of cells in the mitochondrial pathway, and is recruited to the apoptotic body composed of Cyt c/d ATP/Apaf-1. Homologous activation is the earliest hydrolysis activation event of caps in the process of cell apoptosis. After caspase activation is started, the cell death process is started. The downstream caspase is hydrolyzed by heterologous activation to amplify the apoptosis signal, and at the same time, the death signal is transmitted downward. Hetero activation refers to the activation of one caspase and the activation of another caspase, which is a classical way of activating the zymogen of apoptosis protease. Heterogeneously activated caspases are also called executor caspases, including caspase-3, - 6, and - 7. Running Caspase is not like starting Caspase. It cannot be recruited or combined with the initial activation complex. They can only be activated by starting Caspase.