6JLY

eIF2a - eIF2B complex

Summary for 6JLY

• Entry DOI: 10.2210/pdb6jly/pdb
• Descriptor: Translation initiation factor eIF-2B subunit alpha, Probable translation initiation factor eIF-2B subunit beta, Probable translation initiation factor eIF-2B subunit gamma, ... (7 entities in total)
• Functional Keywords: translation initiation, translation
• Biological source: Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast); More
• Total number of polymer chains: 12
• Total formula weight: 590952.62

Authors

Kashiwagi, K.,Ito, T. (deposition date: 2019-03-07, release date: 2019-05-01, Last modification date: 2024-03-27)

Primary citation

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, 364:495-499, 2019

PubMed 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.

PubMed: 31048492
DOI: 10.1126/science.aaw4104

Experimental method

X-RAY DIFFRACTION (3.5 Å)