DOI: 10.1101/503979Dec 21, 2018Paper

Structural basis for the inhibition of translation through eIF2α phosphorylation

BioRxiv : the Preprint Server for Biology
Yuliya GordiyenkoV Ramakrishnan

Abstract

One of the responses to stress by eukaryotic cells is the down-regulation of protein synthesis by phosphorylation of translation initiation factor eIF2. Phosphorylation results in low availability of the eIF2 ternary complex (eIF2-GTP-tRNAi) by affecting its interaction with its GTP-GDP exchange factor eIF2B. We have determined the cryo-EM structure of eIF2B in complex with phosphorylated eIF2 at an overall resolution of 4.15 Å. Two eIF2 molecules bind opposite sides of an eIF2B hetero-decamer through eIF2α-D1, which contains the phosphorylated Ser51. eIF2α-D1 is mainly inserted between the N-terminal helix bundle domains of δ and α subunits of eIF2B. Phosphorylation of Ser51 enhances binding to eIF2B through direct interactions of phosphate groups with residues in eIF2Bα and indirectly by inducing contacts of eIF2α helix 58-63 with eIF2Bδ leading to a competition with Met-tRNAi

Related Concepts

Down-Regulation
Eukaryotic Initiation Factor-2
Glycoprotein Hormones, alpha Subunit
Guanosine Triphosphate
Methionine
Inorganic phosphate
Phosphorylation
Dopamine D1 Receptor
Guanine Nucleotide Exchange Factors
Protein Biosynthesis

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