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-Structure paper
タイトル | Structural basis for eIF2B inhibition in integrated stress response. |
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ジャーナル・号・ページ | Science, Vol. 364, Issue 6439, Page 495-499, Year 2019 |
掲載日 | 2019年5月3日 |
著者 | Kazuhiro Kashiwagi / Takeshi Yokoyama / Madoka Nishimoto / Mari Takahashi / Ayako Sakamoto / Mayumi Yonemochi / Mikako Shirouzu / Takuhiro Ito / |
PubMed 要旨 | 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 ...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. |
リンク | Science / PubMed:31048492 |
手法 | EM (単粒子) / X線回折 |
解像度 | 3.35 - 6.8 Å |
構造データ | EMDB-9842: PDB-6jly: PDB-6jlz: |
化合物 | ChemComp-PO4: |
由来 |
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キーワード | TRANSLATION / Translation Initiation |