Research School of Biology, The Australian National University, Canberra, Australia.
Medical School, The Australian National University, Canberra, Australia.
PLoS Pathog. 2021 Jul 29;17(7):e1009797. doi: 10.1371/journal.ppat.1009797. eCollection 2021 Jul.
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.
辅酶 A 是由泛酸通过五个酶介导的步骤合成的。第一步由泛酸激酶（PanK）催化。迄今为止，所有已鉴定的 PanK 均形成同源二聚体。许多生物体表达多种 PanK。在某些情况下，这些 PanK 并非功能冗余，有些似乎没有功能。在这里，我们研究了两种致病顶复门寄生虫疟原虫和刚地弓形虫中的 PanK。这两种生物体都表达了两种 PanK 同源物（PanK1 和 PanK2）。我们证明 PfPanK1 和 PfPanK2 相互作用，形成一个单一的、功能齐全的 PanK 复合物，其中包括多功能蛋白 Pf14-3-3I。同样，我们证明 TgPanK1 和 TgPanK2 形成具有 PanK 活性的单一复合物。TgPanK1 和 TgPanK2 对刚地弓形虫的增殖都是必不可少的，特别是由于它们的 PanK 活性。我们的研究构成了自然界中异源 PanK 复合物的第一个例子，并为某些生物体中存在多种 PanK 提供了一个解释。
