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Mia40 targets cysteines in a hydrophobic environment to direct oxidative protein folding in the mitochondria

Title data

Koch, Johanna R. ; Schmid, Franz X.:
Mia40 targets cysteines in a hydrophobic environment to direct oxidative protein folding in the mitochondria.
In: Nature Communications. Vol. 5 (2014) . - 3041.
ISSN 2041-1723
DOI: https://doi.org/10.1038/ncomms4041

Abstract in another language

Mia40 catalyses the oxidative folding of disulphide-containing proteins in the mitochondria. The folding pathway is directed by the formation of the first mixed disulphide between Mia40 and its substrate. Here, we employ Cox17 to elucidate the molecular determinants of this reaction. Mia40 engages initially in a dynamic non-covalent enzyme-substrate complex that forms and dissociates within milliseconds. Cys36 of Cox17 forms the mixed disulphide in an extremely rapid reaction that is limited by the preceding complex formation with Mia40. Cys36 reacts much faster than the three other cysteines of Cox17, because it neighbours three hydrophobic residues. Mia40 binds preferentially to hydrophobic regions and the dynamic nature of the non-covalent complex allows rapid reorientation for an optimal positioning of the reactive cysteine. Mia40 thus uses the unique proximity between its substrate-binding site and the catalytic disulphide to select a particular cysteine for forming the critical initial mixed disulphide.

Further data

Item Type: Article in a journal
Refereed: Yes
Additional notes: PubMed-ID: 24407114
Institutions of the University: Faculties
Faculties > Faculty of Biology, Chemistry and Earth Sciences
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors > Professor Biochemistry - Univ.-Prof. Dr. Franz Xaver Schmid
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Professorship Biochemistry
Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors
Result of work at the UBT: Yes
DDC Subjects: 500 Science > 540 Chemistry
Date Deposited: 21 Apr 2015 13:34
Last Modified: 28 Feb 2023 13:55
URI: https://eref.uni-bayreuth.de/id/eprint/10476