論文 - 詳細
| RRC ID | 78364 |
|---|---|
| 著者 | Kamada Y, Umeda C, Mukai Y, Ohtsuka H, Otsubo Y, Yamashita A, Kosugi T. |
| タイトル | Structure-based engineering of Tor complexes reveals that two types of yeast TORC1 produce distinct phenotypes. |
| ジャーナル | J Cell Sci |
| Abstract |
Certain proteins assemble into diverse complex states, each having a distinct and unique function in the cell. Target of rapamycin (Tor) complex 1 (TORC1) plays a central role in signalling pathways that allow cells to respond to the environment, including nutritional status signalling. TORC1 is widely recognised for its association with various diseases. The budding yeast Saccharomyces cerevisiae has two types of TORC1, Tor1-containing TORC1 and Tor2-containing TORC1, which comprise different constituent proteins but are considered to have the same function. Here, we computationally modelled the relevant complex structures and then, based on the structures, rationally engineered a Tor2 mutant that could form Tor complex 2 (TORC2) but not TORC1, resulting in a redesign of the complex states. Functional analysis of the Tor2 mutant revealed that the two types of TORC1 induce different phenotypes, with changes observed in rapamycin, caffeine and pH dependencies of cell growth, as well as in replicative and chronological lifespan. These findings uncovered by a general approach with huge potential - model structure-based engineering - are expected to provide further insights into various fields such as molecular evolution and lifespan. |
| 巻・号 | 137(4) |
| 公開日 | 2024-2-15 |
| DOI | 10.1242/jcs.261625 |
| PII | 344020 |
| PMID | 38415789 |
| MeSH | Mechanistic Target of Rapamycin Complex 1 / genetics Mechanistic Target of Rapamycin Complex 2 Phenotype Saccharomyces cerevisiae* / genetics Saccharomycetales* Sirolimus |
| IF | 4.573 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 12 |
| 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 | BYP9689 |