<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Structural Studies of Variant Surface Glycoproteins on the Trypanosoma Surface"^^ . "Trypanosoma parasites are the pathogenic agent causing human and animal African\r\nTrypanosomiasis. The parasites undergo a process called antigenic variation, which\r\nallows them to perpetually evade the host immune response. Trypanosomes are\r\ncoated almost uniformly with a single protein, the Variant Surface Glycoprotein\r\n(VSG). This protein exists in over 1000 distinct alterations within the genetic repertoire\r\nof the parasite. These highly antigenic membrane proteins will trigger an\r\nextreme immune reaction, which are effective in clearing parasite.\r\nHowever, some cells in the pathogen population will switch to another VSG coat\r\nprotein. This mechanism introduces a novel antigenic surface to the current Ig response,\r\nrendering it non-effective. The first two published protein structures lead\r\nto the assumption that all VSGs’ N-terminal architecture is highly conserved. However,\r\nthese findings are deceptive. Recently published structures revealed that the\r\nN-terminus diverges far more than initially anticipated.\r\nFurthermore, it has been historically proposed that the VSG coat is not penetrable.\r\nHigh-density packing and the initial structural insight lead to the belief\r\nthat only the upper portion of the N-terminal domain was likely to interact with\r\nthe immune system. More recent reviews evaluated the data on this hypothesis\r\nand found that the evidence is lacking, suggesting that the coat is more accessible\r\nthan previously claimed. This thesis aims to map binding epitopes on the VSG\r\nN-terminal domain, using high-resolution crystallographic data of VSG-nanobody\r\ncomplexes. Two epitopes could be verified, but these surprisingly did not occur on\r\nthe upper surface of the VSG protein, but deeply buried. Three nanobodies were\r\nfound to bind 50 Å below the top of protein at the three-helix bundle, and one other\r\nnanobody was found to bind the bottom lobe, 80 Å below the top surface. These\r\nfindings suggest that, indeed, the antigenic surface coat of Trypanosoma parasites\r\nis not an inaccessible “shield”, but rather major parts of the N-terminal domain\r\nare exposed to the immune system. This data challenges the historical view on the\r\nparasite surface organisation and recasts the understanding of the host-pathogen\r\ninteraction in this disease.\r\nFinally, in collaboration with the Engstler lab at the University Würzburg, we\r\nfound that one of these nanobodies has a toxic effect on live parasites. Incubation\r\nwith this nanobody induces high motility inhibition and eventually leads to death\r\nof the parasite. Electron micrographs revealed that the nanobody’s introduction\r\nresults in the creation of excess membrane particles. These particles are likely the\r\nresults of nanobody-induced membrane fission events. These events usually require\r\na dedicated protein machinery paired with high energetic efforts, while the system\r\ndescribed here in vivo is passively driven by protein-protein crowding on the dense\r\nVSG surface."^^ . "2021" . . . . . . . "Alexander"^^ . "Hempelmann"^^ . "Alexander Hempelmann"^^ . . . . . . "Structural Studies of Variant Surface Glycoproteins on the Trypanosoma Surface (PDF)"^^ . . . "phd_hempelmann.pdf"^^ . . . "Structural Studies of Variant Surface Glycoproteins on the Trypanosoma Surface (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Structural Studies of Variant Surface Glycoproteins on the Trypanosoma Surface (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Structural Studies of Variant Surface Glycoproteins on the Trypanosoma Surface (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Structural Studies of Variant Surface Glycoproteins on the Trypanosoma Surface (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Structural Studies of Variant Surface Glycoproteins on the Trypanosoma Surface (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #30037 \n\nStructural Studies of Variant Surface Glycoproteins on the Trypanosoma Surface\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .