| 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
|
| 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) |
