論文 - 詳細
| RRC ID | 50359 |
|---|---|
| 著者 | Esaki M, Islam MT, Tani N, Ogura T. |
| タイトル | Deviation of the typical AAA substrate-threading pore prevents fatal protein degradation in yeast Cdc48. |
| ジャーナル | Sci Rep |
| Abstract |
Yeast Cdc48 is a well-conserved, essential chaperone of ATPases associated with diverse cellular activity (AAA) proteins, which recognizes substrate proteins and modulates their conformations to carry out many cellular processes. However, the fundamental mechanisms underlying the diverse pivotal roles of Cdc48 remain unknown. Almost all AAA proteins form a ring-shaped structure with a conserved aromatic amino acid residue that is essential for proper function. The threading mechanism hypothesis suggests that this residue guides the intrusion of substrate proteins into a narrow pore of the AAA ring, thereby becoming unfolded. By contrast, the aromatic residue in one of the two AAA rings of Cdc48 has been eliminated through evolution. Here, we show that artificial retrieval of this aromatic residue in Cdc48 is lethal, and essential features to support the threading mechanism are required to exhibit the lethal phenotype. In particular, genetic and biochemical analyses of the Cdc48 lethal mutant strongly suggested that when in complex with the 20S proteasome, essential proteins are abnormally forced to thread through the Cdc48 pore to become degraded, which was not detected in wild-type Cdc48. Thus, the widely applicable threading model is less effective for wild-type Cdc48; rather, Cdc48 might function predominantly through an as-yet-undetermined mechanism. |
| 巻・号 | 7(1) |
| ページ | 5475 |
| 公開日 | 2017-7-14 |
| DOI | 10.1038/s41598-017-05806-y |
| PII | 10.1038/s41598-017-05806-y |
| PMID | 28710470 |
| PMC | PMC5511170 |
| MeSH | Adenosine Triphosphatases / metabolism* Amino Acids, Aromatic / genetics Mutation / genetics Phenotype Proteasome Endopeptidase Complex / metabolism Proteolysis* Saccharomyces cerevisiae / metabolism* Saccharomyces cerevisiae Proteins / chemistry Saccharomyces cerevisiae Proteins / genetics Saccharomyces cerevisiae Proteins / metabolism* Substrate Specificity Valosin Containing Protein / chemistry Valosin Containing Protein / genetics Valosin Containing Protein / metabolism* |
| IF | 3.998 |
| 引用数 | 14 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 酵母 | BYP1416 BYP2446 |