A chemistry-based orthogonal enzyme-substrate design strategy for discovery of substrates of protein palmitoyltransferases

ABSTRACT: Attachment of lipids to proteins is a key form of protein modification which intersects with all areas of cellular physiology 1 . Of these, the most pervasive form of protein lipidation is protein S-acylation, also commonly known as protein palmitoylation. Protein palmitoylation is a post-translational modification whereby long chain fatty acids, most typically the 16-carbon palmitic acid, is attached to a cytosol-facing cysteine through a thioester linkage. More than 10% of the proteome is targeted by this modification2, which is catalyzed by members of the zDHHC family of integral membrane enzymes. In humans, there are 23 members of the zDHHC family localized at a variety of organellar membranes as well as the plasma membrane that catalyze protein palmitoylation. Despite having been discovered more than twenty years ago 3 4 the chemistry and biology of many of the zDHHC members remain poorly understood and for several members, few substrates have been characterized. Intriguingly, there are no primary sequence determinants that dictate sites of protein palmitoylation. Cysteines that are proximal to the membrane have a high propensity of being palmitoylated.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell

SUBMITTER: Shelby Auger  

LAB HEAD: Mark, D.

PROVIDER: PXD041525 | Pride | 2023-10-04

REPOSITORIES: Pride