Evolving dual targeting of a prokaryotic protein in yeast
| Autor: | Efrat Burak, Ora Schueler-Furman, Shimon Sheffer, Ohad Yogev, Ophry Pines |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Protein Folding
biology Mitochondrial processing peptidase Sequence Homology Amino Acid Saccharomyces cerevisiae Mutagenesis Citric Acid Cycle Mitochondrion biology.organism_classification medicine.disease_cause Fumarate Hydratase Mitochondria Cytosol Biochemistry Prokaryotic Cells Fumarase Protein targeting Genetics medicine Escherichia coli Protein folding Molecular Biology Gene Ecology Evolution Behavior and Systematics |
| Zdroj: | Molecular biology and evolution. 30(7) |
| ISSN: | 1537-1719 |
| Popis: | Dual targeting is an important and abundant phenomenon. Indeed, we estimate that more than a third of the yeast mitochondrial proteome is dual localized. The enzyme fumarase is a highly conserved protein in all organisms with respect to its sequence, structure, and enzymatic activity. In eukaryotes, it is dual localized to the cytosol and mitochondria. In Saccharomyces cerevisiae, the dual localization of fumarase is achieved by the reverse translocation mechanism; all fumarase molecules harbor a mitochondrial targeting sequence (MTS), are targeted to mitochondria, begin their translocation, and are processed by mitochondrial processing peptidase in the matrix. A subset of these processed fumarase molecules in transit is then fully imported into the matrix, whereas the majority moves back into the cytosol by reverse translocation. The proposed driving force for fumarase distribution is protein folding during import. Here, we asked how reverse translocation could have evolved on a prokaryotic protein that had already acquired expression from the nuclear genome and a targeting sequence. To address this question, we used, as a model, the Escherichia coli FumC Class II fumarase, which is homologous to eukaryotic fumarases (� 58% identity and � 74% similarity to the yeast Fum1). Starting with an exclusively mitochondrial targeted FumC (attached to a strong MTS), we show that two randomly acquired mutations within the prokaryotic FumC sequence are sufficient to cause substantial dual targeting by reverse translocation. In fact, the unmutated MTS-FumC also has some ability to be dual targeted but only at low temperatures. Our results suggest that in this case, evolution of dual targeting by reverse translocation is based on naturally occurring and fortuitously conserved features of fumarase folding. |
| Databáze: | OpenAIRE |
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