| dc.contributor.advisor | Griesinger, Christian Prof. Dr. | |
| dc.contributor.author | Schomburg, Benjamin | |
| dc.date.accessioned | 2015-12-03T10:10:06Z | |
| dc.date.available | 2015-12-03T10:10:06Z | |
| dc.date.issued | 2015-12-03 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0028-865C-0 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-5409 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 572 | de |
| dc.title | Transmembrane Signalling: Structural and Functional Studies on Histidine Kinase CitA | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Griesinger, Christian Prof. Dr. | |
| dc.date.examination | 2015-01-28 | |
| dc.description.abstracteng | Bacteria utilise two component systems (TCS) consisting of a homodimeric receptor histidine
kinase (HK) and a response regulator (RR) as a prevalent mechanism of stimulus
perception and signal transduction. TCSs are key players in the regulation of
metabolism, motility and development, and in addition are crucial for virulence in a number
of pathogenic species. The study of TCSs is therefore motivated by their importance
as a fundamental and widely used signalling system.
In this study, the Geobacillus thermodenitrificans Citrate receptor A (CitA) is used
as a model system for HKs. Free citrate is recognised by a periplasmic PAS (Per-Arnt-
Sim) domain (PASp) and the input signal is then relayed to a second, cytosolic PAS
domain (PASc) before leading to auto-phosphorylation in the conserved kinase core. Even
though the phosphate transfer mechanism of the kinase has been described in depth, signal
transduction across the membrane remains poorly understood. The aim of this PhD
project therefore is to elucidate the signalling mechanism of CitA by means of combining
liquid- and solid-state-NMR spectroscopy with X-ray crystallography.
Our results show a shortening of the C-terminal beta-strand of CitA PASp by one residue
upon citrate binding, potentially exerting a pull on the second transmembrane helix.
The restructuring of the C-terminus of PASp is in agreement with previously published
results on an isolated citrate-binding PAS domain and a piston model for transmembrane
helix motion. Additionally, liposome-embedded CitA constructs for the first time allow
monitoring changes in the cytosol upon periplasmic citrate binding. In the citrate-bound
state, PASc mobility increases, suggesting a constraining role of PASc keeping the kinase
domain in an inactive conformation until CitA is triggered. | de |
| dc.contributor.coReferee | Steinem, Claudia Prof. Dr. | |
| dc.subject.eng | Histidine Kinase | de |
| dc.subject.eng | Solid-State NMR | de |
| dc.subject.eng | Transmembrane Signaling | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0028-865C-0-2 | |
| dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.identifier.ppn | 842118586 | |