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N-Acetylation of secreted proteins is widespread in Apicomplexa and independent of acetyl-CoA transporter AT1

ABSTRACT: Acetyl-CoA critically participates in post-translational modification of proteins, central carbon and lipid metabolism in several compartments of eukaryotic cells. In mammals, the acetyl-CoA transporter 1 (AT1) facilitates the flux of cytosolic acetyl-CoA into the endoplasmic reticulum (ER) enabling the acetylation of proteins of the secretory pathway in concert with dedicated acetyltransferases including Nat8. Homologues of AT1 and Nat8 were identified in the apicomplexan parasites Toxoplasma gondii and Plasmodium berghei. However, the implication of acetyl-CoA pool influx into the ER in acetylation of ER-transiting proteins and their relevance throughout the parasites’ life cycle is unknown. Here, we report proteome-wide analyses, which revealed unprecedented widespread N-terminal acetylation marks of secreted proteins in both parasites. Deletion of the gene coding for AT1 in both parasites, resulted in global loss of fitness and in addition to retardation in erythrocytic development, malaria parasites are blocked in transmission to mosquitoes. However, in absence of AT1 proteome wide lysine and N-terminal acetylation modifications remain unaltered. This highlights a role of AT1 in parasite development uncoupled to acetylation capacity, indicative of an unusually active acetylation machinery occurring in the ER of Apicomplexa.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Toxoplasma Gondii Plasmodium Berghei

SUBMITTER: Jean Baptiste BOYER

LAB HEAD: Carmela GIGLIONE

PROVIDER: PXD029616 | Pride | 2022-06-20

REPOSITORIES: Pride

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