Evolutionary divergent PEX3 is essential for glycosome biogenesis and survival of trypanosomatid parasites

Publication date: Available online 29 July 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell ResearchAuthor(s): Vishal C. Kalel, Mengqiao Li, Stefan Gaussmann, Florent Delhommel, Ann-Britt Schäfer, Bettina Tippler, Martin Jung, Renate Maier, Silke Oeljeklaus, Wolfgang Schliebs, Bettina Warscheid, Michael Sattler, Ralf ErdmannAbstractTrypanosomatid parasites cause devastating African sleeping sickness, Chagas disease, and Leishmaniasis that affect about 18 million people worldwide. Recently, we showed that the biogenesis of glycosomes could be the “Achilles' heel” of trypanosomatids suitable for the development of new therapies against trypanosomiases. This was shown for inhibitors of the import machinery of matrix proteins, while the distinct machinery for the topogenesis of glycosomal membrane proteins evaded investigation due to the lack of a druggable interface. Here we report on the identification of the highly divergent trypanosomal PEX3, a central component of the transport machinery of peroxisomal membrane proteins and the master regulator of peroxisome biogenesis. The trypanosomatid PEX3 shows very low degree of conservation and its identification was made possible by a combinatory approach identifying of PEX19-interacting proteins and secondary structure homology screening. The trypanosomal PEX3 localizes to glycosomes and directly interacts with the membrane protein import receptor PEX19. RNAi-studies revealed that the PEX3 is essential and that ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Cell Research - Category: Molecular Biology Source Type: research