Additional remarks phenotype | Mutant/mutation
The mutant lacks expression of SufS and expresses GFP under the constitutive eef1a promoter.
(bioRxiv preprint doi: https://doi.org/10.1101/833145. this version posted September 14, 2020)
Protein (function)
Iron-sulfur [Fe-S] clusters are inorganic cofactors that are found on proteins from a range of biological processes and are present in most organisms. The assembly of [Fe-S] clusters on apoproteins is not a spontaneous process but is mediated by distinct pathways that mobilise sulfur atoms from L-cysteines, and assemble them onto scaffold components. The scaffold also receives iron from iron donors and the assembled [Fe-S] clusters are transferred to the target apoprotein via carrier protein(s). In bacteria, three distinct sets of factors/enzymes encoded as operons assemble [Fe-S] clusters; the bacterial isc, suf and nif operons encode proteins that are components of the ISC (iron-sulfur cluster formation), SUF (sulfur mobilization) and NIF (nitrogen fixation) assembly systems. The ISC system is the major [Fe-S] biogenesis system with the SUF system being activated under iron starvation or oxidative stress.
In eukaryotes, [Fe-S] assembly systems are thought to have evolved from bacterial endosymbionts. The SUF pathway is found in plastid-containing protozoa and plants. The e apicoplast, the relict plastid of the malaria parasite, harbours a functional SUF pathway. Except apicoplast-encoded SufB in Plasmodium spp., all constituent proteins of the SUF pathway are nuclear-encoded and targeted to the apicoplast. These include the cysteine desulfurase SufS and its interacting partner SufE [18], SufC and SufD that are predicted to constitute the scaffold complex with SufB, and putative carrier proteins SufA and Nfu. Components of the SUF pathway in P. berghei have also been reported to be refractory to gene deletion. Apicoplast proteins that likely require [Fe-S] clusters include ferredoxin, two enzymes (IspG and IspH) of the DOXP pathway of isoprenoid biosynthesis, LipA (lipoic acid synthase), and MiaB (tRNA methylthiotransferase).
Phenotype
Reduced asexual growth/multiplication in mice (33%)
Additional information
Deletion of the SufS in the PQ(R) parasites abolished the impact of the chemosensitizers probenecid, verapamil, or cyproheptadine on lumefantrine (LM) activity, and restored the susceptibility of the PQ(R) parasites to LM.
Other mutants |