PfClpC Is an Essential Clp Chaperone Required for Plastid Integrity and Clp Protease Stability in Plasmodium falciparum
| Autor: | Paul S Kim, Anat Florentin, Michael J. Cipriano, Manuel A. Fierro, Boris Striepen, Jillian D Fishburn, David W. Cobb, Vasant Muralidharan |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Proteases Endopeptidase Clp medicine.medical_treatment Plasmodium falciparum 030106 microbiology Mutant Protozoan Proteins Apicoplasts Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences parasitic diseases Organelle Enzyme Stability medicine Humans Plastid lcsh:QH301-705.5 Gene Cells Cultured Apicoplast Protease biology biology.organism_classification Cell biology 030104 developmental biology lcsh:Biology (General) Essential gene Chaperone (protein) Mutation biology.protein |
| Zdroj: | Cell Reports, Vol 21, Iss 7, Pp 1746-1756 (2017) |
| ISSN: | 2211-1247 |
| Popis: | Summary: The deadly malaria parasite Plasmodium falciparum contains a nonphotosynthetic plastid, known as the apicoplast, that functions to produce essential metabolites, and drugs that target the apicoplast are clinically effective. Several prokaryotic caseinolytic protease (Clp) genes have been identified in the Plasmodium genome. Using phylogenetic analysis, we focused on the Clp members that may form a regulated proteolytic complex in the apicoplast. We genetically targeted members of this complex and generated conditional mutants of the apicoplast-localized PfClpC chaperone and PfClpP protease. Conditional inhibition of the PfClpC chaperone resulted in growth arrest and apicoplast loss and was rescued by addition of the essential apicoplast-derived metabolite IPP. Using a double-conditional mutant parasite line, we discovered that the chaperone activity is required to stabilize the mature protease, revealing functional interactions. These data demonstrate the essential function of PfClpC in maintaining apicoplast integrity and its role in regulating the proteolytic activity of the Clp complex. : Plasmodium falciparum contains a unique organelle, the apicoplast. Using genetic and phenotypic assays, Florentin et al. characterize the apicoplast Clp chaperone and protease. They find that the chaperone is essential for protease stability and that together they function to maintain organelle integrity and segregation into daughter cells. Keywords: malaria, Plasmodium, apicoplast, IPP, Clp, chaperone, caseinolytic protease |
| Databáze: | OpenAIRE |
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