Architecture of a Host–Parasite Interface: Complex Targeting Mechanisms Revealed Through Proteomics

摘要: Surface membrane organization and composition is key to cellular function, proteins serve many essential roles in endocytosis, secretion, cell recognition. The surface of parasitic organisms, however, a double-edged sword; this the primary interface between parasites their hosts, those crucial processes must be carried out while avoiding elimination by host immune defenses. For extracellular African trypanosomes, partitioned such that all endo- exocytosis directed through specific region, flagellar pocket, which it thought majority invariant reside. However, very few these have been identified, severely limiting functional studies, hampering development potential treatments. Here we used an integrated biochemical, proteomic bioinformatic strategy identify components human parasite Trypanosoma brucei. This proteome contains previously known pocket as well multiple novel components, significantly enriched are for survival. Molecules with receptor-like properties almost exclusively parasite-specific, whereas transporter-like conserved model organisms. Validation shows constituents bona fide surface-associated and, expected, most present at pocket. Moreover, largest systematic analysis trypanosome molecules date provides evidence compartmentalized into three distinct domains free diffusion each, but selective, asymmetric traffic between. work paradigm compartmentalization resource its analysis.