A novel heteromeric pantothenate kinase complex in apicomplexan parasites

Erick T Tjhin; Vanessa M Howieson; Christina Spry; Giel G van Dooren; Kevin J Saliba

doi:10.1371/journal.ppat.1009797

A novel heteromeric pantothenate kinase complex in apicomplexan parasites

PLoS Pathog. 2021 Jul 29;17(7):e1009797. doi: 10.1371/journal.ppat.1009797. eCollection 2021 Jul.

Authors

Erick T Tjhin¹, Vanessa M Howieson¹, Christina Spry¹, Giel G van Dooren¹, Kevin J Saliba^{1

2}

Affiliations

¹ Research School of Biology, The Australian National University, Canberra, Australia.
² Medical School, The Australian National University, Canberra, Australia.

Abstract

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 PfPanK1 and PfPanK2 associate, forming a single, functional PanK complex that includes the multi-functional protein, Pf14-3-3I. Similarly, we demonstrate that TgPanK1 and TgPanK2 form a single complex that possesses PanK activity. Both TgPanK1 and TgPanK2 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Isoenzymes
Phosphotransferases (Alcohol Group Acceptor) / chemistry*
Phosphotransferases (Alcohol Group Acceptor) / metabolism*
Plasmodium falciparum / enzymology*
Protozoan Proteins / chemistry
Protozoan Proteins / metabolism
Toxoplasma / enzymology*

Substances

Isoenzymes
Protozoan Proteins
Phosphotransferases (Alcohol Group Acceptor)
pantothenate kinase

Grants and funding

ETT, VMH and CS were supported by Research Training Program scholarships from the Australian Government. CS was also funded by an NHMRC Overseas Biomedical Fellowship (1016357). This work was, in part, supported by a Project Grant (APP1129843) from the National Health and Medical Research Council to KJS and a Discovery Grant (DP150102883) from the Australian Research Council to GvD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.