7KMA
Crystal structure of eif2Balpha with a ligand.
Summary for 7KMA
| Entry DOI | 10.2210/pdb7kma/pdb |
| Related | 3ECS |
| Descriptor | Translation initiation factor eIF-2B subunit alpha, 6-O-phosphono-alpha-D-mannopyranose, ACETATE ION, ... (4 entities in total) |
| Functional Keywords | translation initiation factor eif-2b, translation factor activity, rna binding, translation regulator activity, nucleic acid binding, sugar binding protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 8 |
| Total formula weight | 279444.92 |
| Authors | Nocek, B.,Hao, Q.,Remarcik, C.,Stoll, V.,Wong, Y.,Sidrauski, C. (deposition date: 2020-11-02, release date: 2021-07-21, Last modification date: 2023-10-18) |
| Primary citation | Hao, Q.,Heo, J.M.,Nocek, B.P.,Hicks, K.G.,Stoll, V.S.,Remarcik, C.,Hackett, S.,LeBon, L.,Jain, R.,Eaton, D.,Rutter, J.,Wong, Y.L.,Sidrauski, C. Sugar phosphate activation of the stress sensor eIF2B. Nat Commun, 12:3440-3440, 2021 Cited by PubMed Abstract: The multi-subunit translation initiation factor eIF2B is a control node for protein synthesis. eIF2B activity is canonically modulated through stress-responsive phosphorylation of its substrate eIF2. The eIF2B regulatory subcomplex is evolutionarily related to sugar-metabolizing enzymes, but the biological relevance of this relationship was unknown. To identify natural ligands that might regulate eIF2B, we conduct unbiased binding- and activity-based screens followed by structural studies. We find that sugar phosphates occupy the ancestral catalytic site in the eIF2Bα subunit, promote eIF2B holoenzyme formation and enhance enzymatic activity towards eIF2. A mutant in the eIF2Bα ligand pocket that causes Vanishing White Matter disease fails to engage and is not stimulated by sugar phosphates. These data underscore the importance of allosteric metabolite modulation for proper eIF2B function. We propose that eIF2B evolved to couple nutrient status via sugar phosphate sensing with the rate of protein synthesis, one of the most energetically costly cellular processes. PubMed: 34103529DOI: 10.1038/s41467-021-23836-z PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.7 Å) |
Structure validation
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