Structural investigation of Tc toxin activation

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dc.contributor.advisorRaunser, Stefan
dc.contributor.authorBader, Raphael
dc.contributor.refereeSummerer, Daniel
dc.date.accepted2025-09-11
dc.date.accessioned2025-10-20T08:39:19Z
dc.date.available2025-10-20T08:39:19Z
dc.date.issued2025
dc.description.abstractTc toxins represent a potent class of bacterial protein toxins, with molecular complexes reaching up to 2 MDa. Their exceptional size both protects toxic effectors and makes them one of the largest known protein translocation systems inserting into host membranes. Due to their adaptability, Tc toxins have gained interest for translational applications, including biopesticides and molecular delivery systems. However, the molecular basis of their interaction with host cells remains poorly understood. In this work, I applied an integrative structural biology approach, combining cryo-electron microscopy, cryo-electron tomography, light microscopy, and molecular dynamics simulations, to elucidate Tc toxin function. Using high-resolution structures of Photorhabdus luminescens Tc mutants, we uncovered a conserved mechanism for pH-dependent pore formation, mediated by an electrostatically regulated molecular latch. Further analysis of Yersinia entomophaga Tc (YenTc) revealed novel conformational states, indicating that outer shell rearrangements confer structural versatility across split-A Tc toxins. To connect structural dynamics with cellular activity, I developed a fluorescent reporter assay that monitors endosomal maturation in single cells, enabling direct correlation with electron microscopy imaging of Tc toxin entry. Together, these findings provide molecular insights into Tc toxin action and establish new tools for dissecting their cellular uptake, thereby facilitating future efforts to adapt Tc toxins for biomedical and agricultural applications.en
dc.identifier.urihttp://hdl.handle.net/2003/44038
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-25806
dc.language.isoen
dc.subjectTc toxinsen
dc.subjectStructural biologyen
dc.subjectCryo-EMen
dc.subjectMechanistic insightsen
dc.subjectPore formationen
dc.subjectHost interactionen
dc.subjectInfectionen
dc.subject.ddc570
dc.subject.ddc540
dc.subject.rswkStrukturbiologiede
dc.subject.rswkKryoelektronenmikroskopiede
dc.subject.rswkInfektionde
dc.titleStructural investigation of Tc toxin activationen
dc.typeText
dc.type.publicationtypePhDThesis
dcterms.accessRightsopen access
eldorado.dnb.deposittrue
eldorado.secondarypublicationfalse

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