2020 EJRNL PP Saara-Anne Azizi -1.pdf
Terbatas Irwan Sofiyan
» ITB
Terbatas Irwan Sofiyan
» ITB
While lipids were first appreciated as a critical hydrophobic barrier, our
understanding of their roles at the cellular and organismal levels continues to grow. Not
only are they important independent operators, providing a platform for both static and
dynamic organization and communication within the cell, they also exert significant
effects via the chemical modification of proteins. Addition of a lipid post-translational
modification (PTM) alters protein hydrophobicity and behavior, with distinct
consequences for subcellular trafficking, localization, intra- and intermolecular
interactions, and stability. One of the most abundant and widespread protein lipidation
events is S-acylation, installation of a long-chain lipid to the thiol of a cysteine side chain
through a thioester linkage. S-Acylation is often referred to as S-palmitoylation, due to
the prevalence of palmitate as the lipid modification. Unlike many lipid PTMs, Sacylation
is enzymatically reversible, enabling the cell to tune proteome-wide properties
through dynamic alterations in protein lipidation status. While much has been uncovered
about the molecular effects of S-acylation and its implications for physiology, current
biochemical and chemical methods only assess substrate lipidation levels or steady-state levels of enzyme activity. Yet, the writer protein acyl transferases (PATs) and eraser acyl protein thioesterases (APTs) are dynamically active, responsible for sometimesrapid changes in S-palmitoylation status of target proteins. Thus, to understand the full scope, significance, and subtlety of Sdeacylation and its regulation in the cell, it is necessary to observe the timing and cellular geography of regulatory enzyme activities.