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Characterization of mitochondrion-targeted GTPases in Plasmodium falciparum

Published online by Cambridge University Press:  12 April 2018

Kirti Gupta ,
Ankit Gupta ,
Afreen Haider  and
Saman Habib Open the ORCID record for Saman Habib [Opens in a new window]
Kirti Gupta
Affiliation:
Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Lucknow, India
Ankit Gupta
Affiliation:
Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Lucknow, India
Afreen Haider
Affiliation:
Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Lucknow, India
Saman Habib*
Affiliation:
Division of Molecular and Structural Biology, CSIR-Central Drug Research Institute, Lucknow, India
*
Author for correspondence: Saman Habib, E-mail: saman.habib@gmail.com, saman_habib@cdri.res.in
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Abstract

Ribosome assembly is critical for translation and regulating the response to cellular events and requires a complex interplay of ribosomal RNA and proteins with assembly factors. We investigated putative participants in the biogenesis of the reduced organellar ribosomes of Plasmodium falciparum and identified homologues of two assembly GTPases – EngA and Obg that were found in mitochondria. Both are indispensable in bacteria and P. berghei EngA is among the ‘essential’ parasite blood stage proteins identified recently. PfEngA and PfObg1 interacted with parasite mitoribosomes in vivo. GTP stimulated PfEngA interaction with the 50S subunit of Escherichia coli surrogate ribosomes. Although PfObg1–ribosome interaction was independent of nucleotide binding, GTP hydrolysis by PfObg1 was enhanced upon ribosomal association. An additional function for PfObg1 in mitochondrial DNA transactions was suggested by its specific interaction with the parasite mitochondrial genome in vivo. Deletion analysis revealed that the positively-charged OBG (spoOB-associated GTP-binding protein) domain mediates DNA-binding. A role for PfEngA in mitochondrial genotoxic stress response was indicated by its over-expression upon methyl methanesulfonate-induced DNA damage. PfEngA had lower sensitivity to an E. coli EngA inhibitor suggesting differences with bacterial counterparts. Our results show the involvement of two important GTPases in P. falciparum mitochondrial function, with the first confirmed localization of an EngA homologue in eukaryotic mitochondria.

Keywords

DNA-bindingEngAObgPlasmodium falciparumribosome assembly
Type
Research Article
Information
Parasitology , Volume 145 , Issue 12 , October 2018 , pp. 1600 - 1612
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Copyright
Copyright © Cambridge University Press 2018 

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