Lipid modification of proteins is a widespread, essential process
whereby fatty acids, cholesterol, isoprenoids, phospholipids,
or glycosylphospholipids are attached to polypeptides.
These hydrophobic groups may affect protein structure, function,
localization, and/or stability; as a consequence such modifications
play critical regulatory roles in cellular systems.
Recent advances in chemical biology and proteomics have
allowed the profiling of modified proteins, enabling dissection
of the functional consequences of lipid addition. The
enzymes that mediate lipid modification are specific for both
the lipid and protein substrates, and are conserved from fungi
to humans. In this article we review these enzymes, their substrates,
and the processes involved in eukaryotic lipid modification
of proteins. We further focus on its occurrence in
the fungal pathogen Cryptococcus neoformans, highlighting
unique features that are both relevant for the biology of the
organism and potentially important in the search for new
therapies.
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