Structural basis for the inhibition of translation through eIF2a phosphorylation
Yuliya Gordiyenko, José Luis Llácer, Venki Ramakrishnan
Received Date: 19th December 18
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 eIF2a-D1, which contains the phosphorylated Ser51. eIF2a-D1 is mainly inserted between the N-terminal helix bundle domains of d and a subunits of eIF2B. Phosphorylation of Ser51 enhances binding to eIF2B through direct interactions of phosphate groups with residues in eIF2Ba and indirectly by inducing contacts of eIF2a helix 58-63 with eIF2Bd leading to a competition with Met-tRNAi.
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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.