| dc.contributor.advisor | Rehling, Peter Prof. Dr. | |
| dc.contributor.author | Schendzielorz, Alexander Benjamin | |
| dc.date.accessioned | 2017-12-01T10:26:40Z | |
| dc.date.available | 2017-12-01T10:26:40Z | |
| dc.date.issued | 2017-12-01 | |
| dc.identifier.uri | http://hdl.handle.net/11858/00-1735-0000-0023-3F95-8 | |
| dc.identifier.uri | http://dx.doi.org/10.53846/goediss-6606 | |
| dc.language.iso | eng | de |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.subject.ddc | 572 | de |
| dc.title | Import of proteins along the presequence pathway | de |
| dc.type | doctoralThesis | de |
| dc.contributor.referee | Rehling, Peter Prof. Dr. | |
| dc.date.examination | 2017-11-15 | |
| dc.description.abstracteng | The aim of this study was to investigate the mechanism of protein transport by the
presequence translocase (TIM23) in the inner mitochondrial membrane. Presequencecontaining
proteins are imported through the translocase of the outer membrane
(TOM) complex and handed over to the receptor Tim50 in the inner membrane. The
membrane potential (Δψ) acts on positive charges within the presequence, which
drives initial translocation through the Tim23 channel.
I found that matrix targeted proteins display surprisingly different dependencies on
Δψ. Interestingly, the precursor´s hypersensitivity to a reduction in Δψ was not linked
to the presequence but to the mature part of the protein. The small membrane protein
Pam17 is selectively recruited to the translocase by the presequence receptor Tim50
to promote transport of hypersensitive proteins. Pam17 dissociates from the import
channel once the Hsp70 based import motor takes over driving the precursor in an
ATP-dependent manner. I have therefore identified a second Δψ-dependent step,
which acts on the mature part of the import substrate and takes place after Δψ-driven
translocation of the presequence but prior to ATP-mediated import motor action.
In the second part of the thesis, the molecular function of the channel forming protein
Tim23 was investigated. Conserved residues in the second transmembrane segment
that face the water filled pore were analyzed. Different mutations of these residues led
to reduced cation selectivity and response to presequences of the Tim23 protein and
renders the channel insensitive to substrates. One of these mutations, a N150A
substitution, caused a growth and import defect in yeast. Since stability and assembly
of the mutant Tim23 protein were not compromised, it was concluded that highly
conserved residues in the channel are crucial for substrate affinity in vitro and for
protein import in vivo. | de |
| dc.contributor.coReferee | Rodnina, Marina Prof. Dr. | |
| dc.subject.eng | Mitochondria, Protein import, Presequence, TIM23 | de |
| dc.identifier.urn | urn:nbn:de:gbv:7-11858/00-1735-0000-0023-3F95-8-5 | |
| dc.affiliation.institute | Göttinger Graduiertenschule für Neurowissenschaften, Biophysik und molekulare Biowissenschaften (GGNB) | de |
| dc.subject.gokfull | Biologie (PPN619462639) | de |
| dc.identifier.ppn | 1006650466 | |