論文 - 詳細
| RRC ID | 58308 |
|---|---|
| 著者 | Kashiwagi K, Yokoyama T, Nishimoto M, Takahashi M, Sakamoto A, Yonemochi M, Shirouzu M, Ito T. |
| タイトル | Structural basis for eIF2B inhibition in integrated stress response. |
| ジャーナル | Science |
| Abstract |
A core event in the integrated stress response, an adaptive pathway common to all eukaryotic cells in response to various stress stimuli, is the phosphorylation of eukaryotic translation initiation factor 2 (eIF2). Normally, unphosphorylated eIF2 transfers the methionylated initiator tRNA to the ribosome in a guanosine 5'-triphosphate-dependent manner. By contrast, phosphorylated eIF2 inhibits its specific guanine nucleotide exchange factor, eIF2B. To elucidate how the eIF2 phosphorylation status regulates the eIF2B activity, we determined cryo-electron microscopic and crystallographic structures of eIF2B in complex with unphosphorylated or phosphorylated eIF2. The unphosphorylated and phosphorylated forms of eIF2 bind to eIF2B in completely different manners: the nucleotide exchange-active and -inactive modes, respectively. These structures explain how phosphorylated eIF2 dominantly inhibits the nucleotide exchange activity of eIF2B. |
| 巻・号 | 364(6439) |
| ページ | 495-499 |
| 公開日 | 2019-5-3 |
| DOI | 10.1126/science.aaw4104 |
| PII | 364/6439/495 |
| PMID | 31048492 |
| MeSH | Amino Acid Motifs Cryoelectron Microscopy Eukaryotic Initiation Factor-2 / chemistry* Eukaryotic Initiation Factor-2B / antagonists & inhibitors* Eukaryotic Initiation Factor-2B / chemistry* Eukaryotic Initiation Factor-2B / metabolism Humans Phosphorylation Stress, Physiological* |
| IF | 41.846 |
| 引用数 | 12 |
| 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 | 42 |
| 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 | |
| 遺伝子材料 | pET28-3C-eIF2Ba (RDB17722) pETDuet-eIF2Bd-eIF2Bb (RDB17723) pCOLA-3C-eIF2Be-eIF2Bg (RDB17724) pEBMulti-Neo-human-eIF2alpha (RDB17725) pEBMulti-Neo-human-eIF2beta (RDB17726) pEBMulti-Neo-human-eIF2gamma-FlagHis8 (RDB17727) pEBMulti-Neo-human-CDC123 (RDB17728) |