A novel lipoate attachment enzyme is shared by Plasmodium and Chlamydia species

Gustavo A. Afanador, Alfredo J. Guerra, Russell P. Swift, Ryan E. Rodriguez, David Bartee, Krista A. Matthews, Arne Schön, Ernesto Freire, Caren L. Freel Meyers, Sean T. Prigge

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Lipoate is an essential cofactor for enzymes that are important for central metabolism and other processes. In malaria parasites, scavenged lipoate from the human host is required for survival. The Plasmodium falciparum mitochondrion contains two enzymes (PfLipL1 and PfLipL2) that are responsible for activating mitochondrial proteins through the covalent attachment of lipoate (lipoylation). Lipoylation occurs via a novel redox-gated mechanism that remains poorly understood. We show that PfLipL1 functions as a redox switch that determines which downstream proteins will be activated. Based on the lipoate redox state, PfLipL1 either functions as a canonical lipoate ligase or as a lipoate activating enzyme which works in conjunction with PfLipL2. We demonstrate that PfLipL2 is a lipoyltransferase and is a member of a novel clade of lipoate attachment enzymes. We show that a LipL2 enzyme from Chlamydia trachomatis has similar activity, demonstrating conservation between intracellular pathogens from different phylogenetic kingdoms and supporting the hypothesis that an early ancestor of malaria parasites once contained a chlamydial endosymbiont. Redox-dependent lipoylation may regulate processes such as central metabolism and oxidative defense pathways.

Original languageEnglish (US)
Pages (from-to)439-451
Number of pages13
JournalMolecular Microbiology
Volume106
Issue number3
DOIs
StatePublished - Nov 2017

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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    Afanador, G. A., Guerra, A. J., Swift, R. P., Rodriguez, R. E., Bartee, D., Matthews, K. A., Schön, A., Freire, E., Freel Meyers, C. L., & Prigge, S. T. (2017). A novel lipoate attachment enzyme is shared by Plasmodium and Chlamydia species. Molecular Microbiology, 106(3), 439-451. https://doi.org/10.1111/mmi.13776