An essential endoplasmic reticulum-resident N-acetyltransferase ortholog in Plasmodium falciparum

Alexander J. Polino, Muhammad M. Hasan, Katherine Floyd, Yolotzin Avila-Cruz, Yujuan Yang, Daniel E. Goldberg

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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 thought to be translated into the endoplasmic reticulum (ER), processed by the aspartic protease plasmepsin V and then N-acetylated, despite having no clear access to cytosolic NATs. Here, we used inducible gene deletion and post-transcriptional knockdown to investigate the primary ER-resident NAT candidate, Pf3D7_1437000. We found that it localizes to the ER 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. Despite this, Pf3D7_1437000 depletion impedes parasite development within the host red blood cell and prevents parasites from completing genome replication. Thus, this work provides further proof of N-terminal acetylation of secretory system proteins, a process unique to apicomplexan parasites, but strongly discounts a promising candidate for this post-translational modification.

Original languageEnglish
Article numberjcs260551
JournalJournal of cell science
Volume136
Issue number6
DOIs
StatePublished - Mar 2023

Keywords

  • N-terminal acetylation
  • Parasitology
  • Secretion

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