| dc.contributor.advisor | Ficner, Ralf Prof. Dr. | |
| dc.contributor.author | Sievers, Katharina | |
| dc.date.accessioned | 2023-11-17T18:48:38Z | |
| dc.date.available | 2023-11-25T00:50:10Z | |
| dc.date.issued | 2023-11-17 | |
| dc.identifier.uri | http://resolver.sub.uni-goettingen.de/purl?ediss-11858/14986 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-10207 | |
| dc.format.extent | 145 | de |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
| dc.subject.ddc | 570 | de |
| dc.title | Structural and functional investigation of tRNA guanine transglycosylase | de |
| dc.type | cumulativeThesis | de |
| dc.contributor.referee | Ficner, Ralf Prof. Dr. | |
| dc.date.examination | 2023-06-09 | de |
| dc.description.abstracteng | In this thesis, two novel structures were presented, jointly illuminating dimerization and
tRNA binding by human TGT. A first structure, obtained by X-ray crystallography, allowed
to give a thorough account of the atomic details of the heterodimeric interface as well as
active site recognition of the substrate RNA. The second structure, obtained by single
particle cryo-EM, is the first to show complete tRNA binding by a TGT enzyme of the
bacterial/eukaryotic type, revealing that both TGT subunits are intimately involved in
tRNA binding. Together, these two structures close several knowledge gaps that remained
in the understanding of eukaryotic TGT and the broader TGT family.
Furthermore, insights on TGT flexibility yielded by cryo-EM dataset were expanded on by
solution small-angle X-ray scattering, allowing to move beyond the previously rigid,
crystal-based view on TGT. The structural data of this thesis was further accompanied by
biochemical characterization, focusing on tRNA binding and the association between tRNA
body and non-catalytic subunit. This integrative approach yielded a new understanding of
eukTGT function which, by careful comparison with bacterial and archaeal TGT, was
finally placed in an evolutionary context.
In consequence, the structural biology of eukaryotic TGT and its tRNA complex is now well
characterized. In contrast, TGT subcellular location, regulation and potential transport are
all largely unknown. It remains to be hoped that complimentary approaches will shed light
on these issues in the future and thus grant a full understanding of eukaryotic TGT in its
cellular context. | de |
| dc.contributor.coReferee | Bohnsack, Markus Prof. Dr. | |
| dc.subject.eng | tRNA | de |
| dc.subject.eng | RNA-binding | de |
| dc.subject.eng | crystallography | de |
| dc.subject.eng | RNA-modification | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-ediss-14986-9 | |
| dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.description.embargoed | 2023-11-25 | de |
| dc.identifier.ppn | 1871667313 | |
| dc.notes.confirmationsent | Confirmation sent 2023-11-17T19:45:01 | de |