Open AccessA novel heteromeric pantothenate kinase complex in apicomplexan parasites
Author(s) -
Erick T. Tjhin,
Vanessa M. Howieson,
Christina Spry,
Giel G. van Dooren,
Kevin J. Saliba
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009797
Subject(s) - biology , coenzyme a , biochemistry , plasmodium falciparum , enzyme , immunology , reductase , malaria
Coenzyme A is synthesised from pantothenate via five enzyme-mediated steps. The first step is catalysed by pantothenate kinase (PanK). All PanKs characterised to date form homodimers. Many organisms express multiple PanKs. In some cases, these PanKs are not functionally redundant, and some appear to be non-functional. Here, we investigate the PanKs in two pathogenic apicomplexan parasites, Plasmodium falciparum and Toxoplasma gondii . Each of these organisms express two PanK homologues (PanK1 and PanK2). We demonstrate that Pf PanK1 and Pf PanK2 associate, forming a single, functional PanK complex that includes the multi-functional protein, Pf 14-3-3I. Similarly, we demonstrate that Tg PanK1 and Tg PanK2 form a single complex that possesses PanK activity. Both Tg PanK1 and Tg PanK2 are essential for T . gondii proliferation, specifically due to their PanK activity. Our study constitutes the first examples of heteromeric PanK complexes in nature and provides an explanation for the presence of multiple PanKs within certain organisms.