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Structure paper

TitleStructural basis for eIF2B inhibition in integrated stress response.
Journal, issue, pagesScience, Vol. 364, Issue 6439, Page 495-499, Year 2019
Publish dateMay 3, 2019
AuthorsKazuhiro Kashiwagi / Takeshi Yokoyama / Madoka Nishimoto / Mari Takahashi / Ayako Sakamoto / Mayumi Yonemochi / Mikako Shirouzu / Takuhiro Ito /
PubMed AbstractA 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.
External linksScience / PubMed:31048492
MethodsEM (single particle) / X-ray diffraction
Resolution3.35 - 6.8 Å
Structure data

9840

6k71

EMDB-9840, PDB-6k71:
eIF2 - eIF2B complex
Method: EM (single particle) / Resolution: 4.3 Å

9841

6k72

EMDB-9841, PDB-6k72:
eIF2(aP) - eIF2B complex
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-9842:
eIF2 - eIF2B (2 molecule)
Method: EM (single particle) / Resolution: 6.8 Å

PDB-6jly:
eIF2a - eIF2B complex
Method: X-RAY DIFFRACTION / Resolution: 3.5 Å

PDB-6jlz:
P-eIF2a - eIF2B complex
Method: X-RAY DIFFRACTION / Resolution: 3.35 Å

Chemicals

ChemComp-PO4:
PHOSPHATE ION

Source
  • homo sapiens (human)
  • schizosaccharomyces pombe (strain 972 / atcc 24843) (yeast)
  • saccharomyces cerevisiae (strain atcc 204508 / s288c) (yeast)
KeywordsTRANSLATION / Translation Initiation

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