Structural and functional characterization of an iron-sulfur cluster assembly scaffold protein-SufA from Plasmodium vivax.
Iron-sulfur (Fe-S) clusters are utilized as prosthetic groups in all living organisms for diverse range of cellular processes including electron transport in respiration and photosynthesis, sensing of ambient conditions, regulation of gene expression and catalysis. In Plasmodium, two Fe-S cluster biogenesis pathways are reported, of which the Suf pathway in the apicoplast has been shown essential for the erythrocytic stages of the parasite. While the initial components of this pathway detailing the sulfur mobilization have been elucidated, the components required for the assembly and transfer of Fe-S clusters are not reported from the parasite. In Escherichia coli, SufB acts as a scaffold protein and SufA traffics the assembled Fe-S cluster from SufB to target apo-proteins. However, in Plasmodium, the homologs of these proteins are yet to be characterized for their function. Here, we report a putative SufA protein from Plasmodium vivax with signature motifs of A-type scaffold proteins, which is evolutionarily conserved. The presence of the [Fe4S4](3+) cluster under reduced conditions was confirmed by UV-visible and EPR spectroscopy and the interaction of these clusters with the conserved cysteine residues of chains A and B of PvSufA, validates its existence as a dimer, similar to that in E. coli. The H-bond interactions at the PvSufA-SufB interface demonstrate SufA as a scaffold protein in conjunction with SufB for the pre-assembly of Fe-S clusters and their transfer to the target proteins. Co-localization of the protein to the apicoplast further provides an experimental evidence of a functional scaffold protein SufA for the biogenesis of Fe-S clusters in apicoplast of Plasmodium.
['Pala|Zarna Rajeshkumar|ZR|', 'Saxena|Vishal|V|', 'Saggu|Gagandeep Singh|GS|', 'Yadav|Sushil Kumar|SK|', 'Pareek|R P|RP|', 'Kochar|Sanjay Kumar|SK|', 'Kochar|Dhanpat Kumar|DK|', 'Garg|Shilpi|S|']
D000595:Amino Acid Sequence D001483:Base Sequence D053898:Biosynthetic Pathways D002352:Carrier Proteins D004926:Escherichia coli D029968:Escherichia coli Proteins D006801:Humans D007506:Iron-Sulfur Proteins D008958:Models, Molecular D010966:Plasmodium vivax D017434:Protein Structure, Tertiary D021381:Protein Transport D016415:Sequence Alignment D017422:Sequence Analysis, DNA
Suf pathway Apicoplast Clinical isolates Immunofluorescence