An essential ER-resident N-acetyltransferase in Plasmodium falciparum

Abstract

N-terminal acetylation is a common eukaryotic protein modification that involves the addition of an acetyl group to the N-terminus of a polypeptide. This modification is largely performed by cytosolic N-terminal acetyltransferases (NATs). Most associate with the ribosome, acetylating nascent polypeptides co-translationally. In the malaria parasite Plasmodium falciparum, exported effectors are translated into the ER, processed by the aspartic protease plasmepsin V and then N-acetylated, despite having no clear access to cytosolic NATs. Here, we used post-transcriptional knockdown to investigate the most obvious candidate, Pf3D7_1437000. We found that it co-localizes with the ER-resident plasmepsin V and is required for parasite growth. However, depletion of Pf3D7_1437000 had no effect on protein export or acetylation of the exported proteins HRP2 and HRP3. Pf3D7_1437000-depleted parasites arrested later in their development cycle than export-blocked parasites, suggesting the proteins essential role is distinct from protein export.