Structural highlights
6jlz is a 12 chain structure with sequence from Baker's yeast and Fission yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | |
| NonStd Res: | |
| Gene: | tif221, SPCC11E10.07c (Fission yeast), tif222, SPAC343.14c (Fission yeast), tif223, SPAC4D7.09 (Fission yeast), tif224, SPAC21E11.06 (Fission yeast), tif225, SPAC8C9.15c (Fission yeast), SUI2, TIF211, YJR007W, J1429 (Baker's yeast) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[IF2A_YEAST] eIF-2 functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S preinitiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B. [EI2BD_SCHPO] Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. [EI2BA_SCHPO] Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. [EI2BG_SCHPO] Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. [EI2BB_SCHPO] Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP. [EI2BE_SCHPO] Subunit of the guanine nucleotide exchange factor for eIF-2.
Publication Abstract from PubMed
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.
Structural basis for eIF2B inhibition in integrated stress response.,Kashiwagi K, Yokoyama T, Nishimoto M, Takahashi M, Sakamoto A, Yonemochi M, Shirouzu M, Ito T Science. 2019 May 3;364(6439):495-499. doi: 10.1126/science.aaw4104. PMID:31048492[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kashiwagi K, Yokoyama T, Nishimoto M, Takahashi M, Sakamoto A, Yonemochi M, Shirouzu M, Ito T. Structural basis for eIF2B inhibition in integrated stress response. Science. 2019 May 3;364(6439):495-499. doi: 10.1126/science.aaw4104. PMID:31048492 doi:http://dx.doi.org/10.1126/science.aaw4104
