Kinase-associated endopeptidase 1 (Kae1) participates in an atypical ribosome-associated complex in the apicoplast of Plasmodium falciparum

Jeremy P. Mallari, Anna Oksman, Barbara Vaupel, Daniel E. Goldberg

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The universally conserved kinase-associated endopeptidase 1 (Kae1) protein family has established roles in N6-threonylcarbamoyl adenosine tRNA modification, transcriptional regulation, and telomere homeostasis. These functions are performed in complex with a conserved core of protein binding partners. Herein we describe the localization, essentiality, and protein-protein interactions for Kae1 in the human malaria parasite Plasmodium falciparum. We found that the parasite expresses one Kae1 protein in the cytoplasm and a second protein in the apicoplast, a chloroplast remnant organelle involved in fatty acid, heme, and isoprenoid biosynthesis. To analyze the protein interaction networks for both Kae1 pathways, we developed a new proteomic cross-validation approach. This strategy compares immunoprecipitation-MS data sets across different cellular compartments to enrich for biologically relevant protein interactions. Our results show that cytoplasmic Kae1 forms a complex with Bud32 and Cgi121 as in other organisms, whereas apicoplast Kae1 makes novel interactions with multiple proteins in the apicoplast. Quantitative RT-PCR and immunoprecipitation studies indicate that apicoplast Kae1 and its partners interact specifically with the apicoplast ribosomes and with proteins involved in ribosome function. Together, these data indicate an expanded, apicoplast-specific role for Kae1 in the parasite.

Original languageEnglish
Pages (from-to)30025-30039
Number of pages15
JournalJournal of Biological Chemistry
Volume289
Issue number43
DOIs
StatePublished - Oct 24 2014

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