7L7G
Electron cryo-microscopy of the eukaryotic translation initiation factor 2B from Homo sapiens (updated model of PDB ID: 6CAJ)
Summary for 7L7G
| Entry DOI | 10.2210/pdb7l7g/pdb |
| Related | 6CAJ |
| EMDB information | 7443 |
| Descriptor | Translation initiation factor eIF-2B subunit epsilon, Translation initiation factor eIF-2B subunit gamma, Translation initiation factor eIF-2B subunit beta, ... (6 entities in total) |
| Functional Keywords | translation; integrated stress response, translation |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 10 |
| Total formula weight | 526770.76 |
| Authors | Tsai, J.C.,Miller-Vedam, L.E.,Anand, A.,Jaishankar, P.,Nguyen, H.C.,Wang, L.,Renslo, A.R.,Frost, A.,Walter, P. (deposition date: 2020-12-28, release date: 2021-03-24, Last modification date: 2024-03-06) |
| Primary citation | Schoof, M.,Boone, M.,Wang, L.,Lawrence, R.,Frost, A.,Walter, P. eIF2B conformation and assembly state regulates the integrated stress response. Elife, 10:-, 2021 Cited by PubMed Abstract: The integrated stress response (ISR) is activated by phosphorylation of the translation initiation factor eIF2 in response to various stress conditions. Phosphorylated eIF2 (eIF2-P) inhibits eIF2's nucleotide exchange factor eIF2B, a twofold symmetric heterodecamer assembled from subcomplexes. Here, we monitor and manipulate eIF2B assembly in vitro and in vivo. In the absence of eIF2B's α-subunit, the ISR is induced because unassembled eIF2B tetramer subcomplexes accumulate in cells. Upon addition of the small-molecule ISR inhibitor ISRIB, eIF2B tetramers assemble into active octamers. Surprisingly, ISRIB inhibits the ISR even in the context of fully assembled eIF2B decamers, revealing allosteric communication between the physically distant eIF2, eIF2-P, and ISRIB binding sites. Cryo-electron microscopy structures suggest a rocking motion in eIF2B that couples these binding sites. eIF2-P binding converts eIF2B decamers into 'conjoined tetramers' with diminished substrate binding and enzymatic activity. Canonical eIF2-P-driven ISR activation thus arises due to this change in eIF2B's conformational state. PubMed: 33688831DOI: 10.7554/eLife.65703 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3 Å) |
Structure validation
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