Like most biochemical processes in the cell, protein S-acylation is reversible to regulate the functions of acylated proteins. S-acylation is reversed by the enzymes acyl protein thioesterases (APTs).

To do their work, APTs have to interact with the lipid membranes that their target proteins are bound to. But even though APTs are central to the important acylation deacylation process little is known about how APTs carry out their functions.

Scientists led by Gisou van der Goot and Matteo Dal Peraro at the EPFL School of Life Sciences have now made significant inroads into our understanding of how APT2, a major acyl thioesterase in the cell, works. The work is published in Nature Chemical Biology.

First, the researchers showed that APTs have intrinsic membrane-binding capacity. Combining X-ray crystallography and molecular dynamics simulations, they showed that APTs contain in their structure positively-charged patches that allow them to electrostatically attract the lipid bilayer of a membrane.