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| Identifier |
000348620 |
| Title |
Οξειδωτική αναδίπλωση πρωτεϊνών στο διαμεμβρανικό χώρο μιτοχονδρίων σακχαρομύκητα |
| Alternative Title |
Οxidative-mediated folding in the intermembrane space of yeast mitochondria |
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Author
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Σιδέρη, Διονυσία-Πολυξένη
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Thesis advisor
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Τοκατλίδης, Κ.
Οικονόμου, Α
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| Abstract |
The intermembrane space of mitochondria (IMS) harbours a dedicated machinery that
promotes the oxidative folding of substrate proteins. The newly identified oxidative pathway consists of the redox-regulated receptor Mia40 and the sulfhydryl oxidase Erv1. Precursors destined to the IMS are trapped by a disulfide relay mechanism which involves an electron cascade from the incoming substrate to Mia40, then on to
Erv1 and finally to molecular oxygen via cytochrome c. This thiol-disulfide exchange mechanism is essential for the import and oxidative folding of the incoming cysteinerich proteins.
In this work we aim to elucidate the mechanistic parameters that define the interaction between the substrate and the oxidase Mia40. Biochemical analysis reveals a general mechanism whereby Mia40 transfers oxidising equivalents to the substrates via an Nterminal
CPC motif. Structural analysis uncovered a hydrophobic cleft in the vicinity of the active site of Mia40 that is used as a substrate binding domain. Furthermore, in organello import experiments have revealed a site-specific mechanism for the
cysteine dependent interaction of Mia40 with the incoming substrate. A unique
cysteine is responsible for docking the protein onto Mia40 that differs depending on the substrate. We further identify the signal responsible for targeting the precursors to
the IMS. Finally we show that this signal directs the docking cysteine of the substrate in the vicinity of the catalytic center of Mia40 via hydrophobic interactions. The present results are an important step towards revealing the full molecular details underlying the oxidative protein folding pathway in mitochondria.
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| Language |
Greek |
| Subject |
Disulfide relay |
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Electron cascade |
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Μεταφορά ηλεκτρονίων |
| Issue date |
2009-07-10 |
| Collection
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School/Department--School of Sciences and Engineering--Department of Biology--Doctoral theses
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Type of Work--Doctoral theses
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| Views |
236 |
Οξειδωτική αναδίπλωση πρωτεϊνών στο διαμεμβρανικό χώρο μιτοχονδρίων σακχαρομύκητα
