期刊
FEBS JOURNAL
卷 280, 期 20, 页码 4960-4969出版社
WILEY-BLACKWELL
DOI: 10.1111/febs.12482
关键词
biogenesis; mitochondria; Erv1; import; Mia40
资金
- IMBB-FORTH
- University of Crete
- European Union (European Social Fund)
- Operational Program 'Education and Lifelong Learning' of the National Strategic Reference Framework Research Funding Program THALES
- Greek General Secretariat for Research and Technology program ARISTEIA
The discovery of the mitochondrial intermembrane space assembly (MIA) pathway was followed by studies that focused mainly on the typical small substrates of this disulfide relay system and the interactions between its two central partners: the oxidoreductase Mia40 and the FAD-protein Erv1. Recent studies have revealed that more complex proteins utilize this pathway, including Mia40 itself. In the present study, we dissect the Mia40 biogenesis in distinct stages, supporting a kinetically coordinated sequence of events, starting with (a) import and insertion through the Tim23 translocon, followed by (b) folding of the core of imported Mia40 assisted by the endogenous Mia40 and (c) final interaction with Erv1. The interaction with endogenous Mia40 and the subsequent interaction with Erv1 represent kinetically distinguishable steps that rely on completely different determinants. Interaction with Mia40 proceeds very early (within 30s) and is characterized by no Cys-specificity, an increased tolerance to mutations of the hydrophobic substrate-binding cleft and no apparent dependence on glutathione as a proofreading mechanism. All of these features illustrate a very atypical behaviour for the Mia40 precursor compared to other substrates of the MIA pathway. By contrast, interaction with Erv1 occurs after 5min of import and relies on a more stringent specificity.
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