bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown
Published: Oct. 14, 2023
Infections by trypanosomatid parasites cause Chagas disease, Human African Trypanosomiasis, and Leishmaniasis, affecting over 12 million people worldwide. Glycosomes, the unique peroxisome-related organelles of trypanosomes are essential for their survival, hence metabolic functions biogenesis mediated peroxins (PEX) suitable as drug targets. Here we report on a comprehensive protein inventory glycosomal membranes through advanced subcellular membrane profiling employing quantitative mass spectrometry. Our analysis resulted in identification 28 novel high confidence proteins. in-depth serves an important resource characterizing glycosome biology development. We validated four so far unknown proteins, including two tail-anchored (TA) homolog human peroxisomal PXMP4, Macrodomain-containing protein. Using structure-based approach, identified one TA proteins long-sought Trypanosoma PEX15. Despite its low sequence similarity, PEX15 exhibits structural topological similarities with yeast (Pex15) counterparts (PEX26). show that is integral interacts PEX6. Accordingly, RNAi knockdown bloodstream form demonstrates it parasite survival. Considering degree conservation counterpart, promising molecular target
Language: Английский