5b04
From Proteopedia
Crystal structure of the eukaryotic translation initiation factor 2B from Schizosaccharomyces pombe
Structural highlights
Function[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 PubMedEukaryotic cells restrict protein synthesis under various stress conditions, by inhibiting the eukaryotic translation initiation factor 2B (eIF2B). eIF2B is the guanine nucleotide exchange factor for eIF2, a heterotrimeric G protein consisting of alpha-, beta- and gamma-subunits. eIF2B exchanges GDP for GTP on the gamma-subunit of eIF2 (eIF2gamma), and is inhibited by stress-induced phosphorylation of eIF2alpha. eIF2B is a heterodecameric complex of two copies each of the alpha-, beta-, gamma-, delta- and epsilon-subunits; its alpha-, beta- and delta-subunits constitute the regulatory subcomplex, while the gamma- and epsilon-subunits form the catalytic subcomplex. The three-dimensional structure of the entire eIF2B complex has not been determined. Here we present the crystal structure of Schizosaccharomyces pombe eIF2B with an unprecedented subunit arrangement, in which the alpha2beta2delta2 hexameric regulatory subcomplex binds two gammaepsilon dimeric catalytic subcomplexes on its opposite sides. A structure-based in vitro analysis by a surface-scanning site-directed photo-cross-linking method identified the eIF2alpha-binding and eIF2gamma-binding interfaces, located far apart on the regulatory and catalytic subcomplexes, respectively. The eIF2gamma-binding interface is located close to the conserved 'NF motif', which is important for nucleotide exchange. A structural model was constructed for the complex of eIF2B with phosphorylated eIF2alpha, which binds to eIF2B more strongly than the unphosphorylated form. These results indicate that the eIF2alpha phosphorylation generates the 'nonproductive' eIF2-eIF2B complex, which prevents nucleotide exchange on eIF2gamma, and thus provide a structural framework for the eIF2B-mediated mechanism of stress-induced translational control. Crystal structure of eukaryotic translation initiation factor 2B.,Kashiwagi K, Takahashi M, Nishimoto M, Hiyama TB, Higo T, Umehara T, Sakamoto K, Ito T, Yokoyama S Nature. 2016 Mar 3;531(7592):122-5. doi: 10.1038/nature16991. Epub 2016 Feb 22. PMID:26901872[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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