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[Fe–S] cluster assembly in the apicoplast and its indispensability in mosquito stages of the malaria parasite
Author(s) -
Charan Manish,
Choudhary Hadi Hasan,
Singh Nidhi,
Sadik Mohammad,
Siddiqi Mohammad Imran,
Mishra Satish,
Habib Saman
Publication year - 2017
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14159
Subject(s) - apicoplast , malaria , parasite hosting , cluster (spacecraft) , plasmodium falciparum , virology , biology , apicomplexa , computer science , immunology , world wide web , programming language
The relict plastid (apicoplast) of the malaria parasite is the site for important biochemical pathways and is essential for parasite survival. The sulfur mobilization ( SUF ) pathway of iron–sulfur [Fe–S] cluster assembly in the apicoplast of Plasmodium spp. is of interest due to its absence in the human host suggesting the possibility of antimalarial intervention through apicoplast [Fe–S] biogenesis. We report biochemical characterization of components of the Plasmodium falciparum apicoplast SUF pathway after the first step of SUF. In vitro interaction experiments and in vivo cross‐linking showed that apicoplast‐encoded Pf SufB and apicoplast‐targeted Pf SufC and Pf SufD formed a complex. The Pf SufB‐C 2 ‐D complex could function as a scaffold to assemble [4Fe–4S] clusters in vitro and activity of the Pf SufC ATP ase was enhanced by Pf SufD. Two carrier proteins, the NifU‐like protein Pf Nfu and the A‐type carrier Pf SufA are homodimers, the former mediating transfer of [4Fe–4S] from the scaffold to a model [4Fe–4S] target protein with higher efficiency. Conditional knockout of SufS, the enzyme catalyzing the first step of SUF, by selective excision in the mosquito stages of Plasmodium berghei severely impaired development of sporozoites in oocysts establishing essentiality of the SUF machinery in the vector. Our results delineate steps of the complete apicoplast SUF pathway and demonstrate its critical role in the parasite life cycle.