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Published on: August 10, 2021
Intrinsically disordered proteins in human mitochondria
Masahiro Ito1, Yukako Tohsato, Hitoshi Sugisawa
1Department of Bioinformatics, College of Life Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan.
Abstract:
Intrinsically disordered (ID) proteins (IDPs) are abundant in eukaryotes but are scarce in prokaryotes. Mitochondria, cellular organelles that descended from Rickettsia-like α-proteobacteria, are at the intersection between prokaryotes and eukaryotes. Although IDPs are reportedly as rare in mitochondria as in bacteria, these details remained to be clarified. Human mitochondrial proteins (n = 706) were obtained from the UniProt database, and information on ID regions of all human proteins was extracted from the DICHOT database. A BLAST search carried out against all α-proteobacterial proteins identified two types of mitochondrial proteins: those with (B) and without (E) bacterial homologues. The B-type proteins (n = 387) descended from a bacterial ancestor, whereas the E-type proteins (n = 319) were more recently added to the mitochondria via the host cell during the early evolution of eukaryotes. The average ID ratios of B-type/E-type proteins are 10.3% and 21.4%, respectively. The 706 proteins were further classified into four groups based on the mitochondrial subcompartment, namely, the matrix, intermembrane space, inner membrane, or outer membrane. The ID ratios in these different locations suggest that the frequency of IDPs in mitochondria might be due to the evolutionary origin (B-type/E-type) of the protein, rather than differences in its functional environment.
Insights
Intrinsically disordered proteins (IDPs) are less common in mitochondria than in eukaryotes, with bacterial-like proteins showing lower disorder than host-derived ones. This suggests evolutionary origin, not location, influences IDP prevalence in mitochondria.
Area of Science:
- Mitochondrial Biology
- Protein Science
- Evolutionary Biology
Background:
- Intrinsically disordered proteins (IDPs) are prevalent in eukaryotes but rare in prokaryotes.
- Mitochondria, originating from α-proteobacteria, represent an evolutionary link between prokaryotes and eukaryotes.
- The abundance of IDPs within mitochondria requires clarification due to their unique evolutionary position.
Purpose of the Study:
- To investigate the prevalence and characteristics of intrinsically disordered proteins (IDPs) in human mitochondria.
- To determine if the evolutionary origin of mitochondrial proteins influences their intrinsic disorder content.
- To compare IDP levels in mitochondrially-encoded proteins versus host-encoded proteins within mitochondria.
Main Methods:
- Retrieved 706 human mitochondrial proteins from UniProt.
- Extracted intrinsically disordered region information using the DICHOT database.
- Performed BLAST searches against α-proteobacterial proteins to classify mitochondrial proteins into bacterial-descended (B-type) and host-derived (E-type).
Main Results:
- Identified 387 B-type and 319 E-type mitochondrial proteins.
- Observed significantly lower average ID ratios in B-type proteins (10.3%) compared to E-type proteins (21.4%).
- Found no strong correlation between mitochondrial subcompartment and IDP ratios, suggesting evolutionary origin is a key factor.
Conclusions:
- The evolutionary origin of mitochondrial proteins significantly impacts their intrinsic disorder content.
- Bacterial-derived mitochondrial proteins exhibit less intrinsic disorder than those acquired later from the host.
- Intrinsic disorder prevalence in mitochondria is primarily shaped by evolutionary history rather than functional localization.
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