Fig. 3

Catalytic mechanisms of DHHC palmitoyl S-acyltransferases (DHHC-PATs) and depalmitoylases. Some DHHC-PATs go through two steps (ping-pong kinetic mechanisms) to catalyse substrate protein S-palmitoylation. First, DHHC-PAT undergoes autopalmitoylation, linking palmitoyl-CoA to Cys156 in the DHHC domain to form an acyl-enzyme transfer intermediate. Subsequently, the palmitoyl chain is transferred to the putative cysteine residue on the substrate protein to complete S-palmitoylation. For depalmitoylases, three categories of depalmitoylases are subject to being palmitoylated to arrive at proper positions to function. A portion of palmitoylated APT1 and APT2 localise to the Golgi, and APT1 is capable of depalmitoylating itself and APT2, which allows them to be released into the cytosol to ensure the steady-state distribution of APTs in the Golgi and the cytosol. A large proportion of palmitoylated proteins are depalmitoylated by APT1 and APT2 on the plasma membrane or in the cytosol. Some palmitoylated proteins on the plasma membrane could also be depalmitoylated by ABHDs. PPT1 and PPT2 are mainly responsible for depalmitoylation of substrate proteins that localise in lysosomes. There are two fates for substrate proteins after depalmitoylation. One of them returns to catalytic positions, such as the Golgi, to undergo repalmitoylation, and the other enters the lysosome to be degraded