An Apicoplast Localized Ubiquitylation System Is Required for the Import of Nuclear-encoded Plastid Proteins

PLoS Pathogens

Giel G. van Dooren¹  Elisadra M. Rodrigues¹  Duk-Won D. Chung²  John C. Tan²  Carrie F. Brooks²  Nadia Ponts²  Karine G. Le Roch³  Swati Agrawal³  Michael T. Ferdig⁴  Boris Striepen⁴  Jacques Prudhomme⁵ 

[1] Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, United States of America;Department of Cell Biology and Neuroscience, University of California, Riverside, California, United States of America;Department of Cellular Biology, University of Georgia, Athens, Georgia, United States of America;Eck Institute of Global Health, University of Notre Dame, South Bend, Indiana, United States of America;Research School of Biology, Australian National University, Canberra, Australia

关键词: Plasmodium;    Toxoplasma gondii;    Recombinant proteins;    Plastids;    Apicomplexa;    Algae;    Cellular structures;    organelles;    Genetic loci;   

DOI  :  10.1371/journal.ppat.1003426

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Apicomplexan parasites are responsible for numerous important human diseases including toxoplasmosis, cryptosporidiosis, and most importantly malaria. There is a constant need for new antimalarials, and one of most keenly pursued drug targets is an ancient algal endosymbiont, the apicoplast. The apicoplast is essential for parasite survival, and several aspects of its metabolism and maintenance have been validated as targets of anti-parasitic drug treatment. Most apicoplast proteins are nuclear encoded and have to be imported into the organelle. Recently, a protein translocon typically required for endoplasmic reticulum associated protein degradation (ERAD) has been proposed to act in apicoplast protein import. Here, we show ubiquitylation to be a conserved and essential component of this process. We identify apicoplast localized ubiquitin activating, conjugating and ligating enzymes in Toxoplasma gondii and Plasmodium falciparum and observe biochemical activity by in vitro reconstitution. Using conditional gene ablation and complementation analysis we link this activity to apicoplast protein import and parasite survival. Our studies suggest ubiquitylation to be a mechanistic requirement of apicoplast protein import independent to the proteasomal degradation pathway.

【 授权许可】

CC BY