Publikationsserver der Universitätsbibliothek Marburg
Titel:Charakterisierung der Dolichol‑Phosphat‑Mannosyltransferase 1, ein Enzym der Biosynthese von Glykosylphosphatidylinositolen im Einzeller Babesia microti
Autor:Stahl, Philipp
Weitere Beteiligte: Schwarz, Ralph Thomas (Prof. Dr.)
Veröffentlicht:2016
URI:https://archiv.ub.uni-marburg.de/diss/z2016/0788
DOI: https://doi.org/10.17192/z2016.0788
URN: urn:nbn:de:hebis:04-z2016-07887
DDC: Biowissenschaften, Biologie
Titel (trans.):Characterization of the Dolichole‑Phosphate‑Mannosyltransferase 1, an enzyme of the biosynthesis of glycosylphosphatidylinositoles in the protozoan Babesia microti
Publikationsdatum:2016-11-30
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
Babesia microti, GPI, Babesia, GPI, Bioinformatik, Hefezellen, Babesia, Babesiose, Komplementation, GPI, DPM1, Phylogenie, Babesiosis, funghi, DPM1, yeast, Hefeartige Pilze, Babesiose, complementation

Zusammenfassung:
Als humane Babesiose bezeichnet man eine durch die Einzeller Babesia divergens und Babesia microti hervorgerufene Infektionskrankheit. Diese eukaryotischen Parasiten werden durch Zecken der Gattung Ixodes übertragen und verursachen Infektionen und Erkrankungen bei einer Vielzahl von Säugetieren, sowie auch beim Menschen. Neben akuten grippeähnlichen Symptomen sind auch latente Verläufe mit monatelanger a‑ oder oligosymptomatischer Parasitämie beschrieben worden. Die Diagnose erfolgt durch den Nachweis der intraerythrozytären Parasiten im Blutausstrich oder im Dicken Tropfen, wobei insbesondere bei geringer Parasitämie die Abgrenzung von einer Malaria sehr schwierig sein kann. Das Enzym Dolichol-Phosphat-Mannosyltransferase 1 (DPM1) ist ein ubiquitär und evolutionär stark konserviertes Enzym und bildet ein essentielles Substrat (Dolichol-Phosphat-Mannose), was für die Biosynthese von Glykosylphosphatidylinositolen (GPIs) im endoplasmatischen Retikulum (ER) unentbehrlich ist. In dieser Arbeit wurde das Protein DPM1 von Babesia microti (B. microti) zu dem bislang nur wenige Informationen vorliegen, hinsichtlich seiner evolutionären Konservierung und seiner genetischen Eigenschaften mithilfe molekularbiologischer und bioinformatischer Techniken in systematischen Schritten charakterisiert. Es konnte gezeigt werden, dass sich DMP1 aus Babesia microti im Vergleich zu einer Vielzahl anderer Organismen unterscheidet. Mittels bioinformatischer Analysen von DPM1 aus Babesia microti, konnte anhand eines phylogenetischen Stammbaums gezeigt werden, dass es sich in puncto Hydrophobizität, vom Vorhandensein von weiteren Hilfsproteinen der DPM-Familie, einer GPI‑Verankerung sowie von Signalpeptidspaltungsstellen von DPM1 der verglichenen Organismen unterscheidet. Insbesondere zu DPM1 aus der Hefe Saccharomyces cerevisiae (S. cerevisiae) bestehen relevante biochemische Unterschiede. Es konnte dennoch mithilfe molekularbiologischer Klonierungstechniken die funktionelle Komplementation von DPM1 in der DPM1‑defizienten‑S. cerevisiae-Mutante, für die DPM1 essentiell ist, mit parasitischem DPM1 nachgewiesen werden. Das zeigt die artunabhängige evolutionäre Konservierung dieses Proteins sowie dessen funktionelle Austauschbarkeit.

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