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. Author manuscript; available in PMC: 2022 Apr 11.
Published in final edited form as: Science. 2020 Apr 24;368(6489):eaat5314. doi: 10.1126/science.aat5314

Fig. 2. The structure and assembly of eIF2B.

Fig. 2.

(A) Top view of the human eIF2B decamer bound to ISRIB. The cryo-EM density at a resolution of 2.7 Å shows ISRIB bound in a deep central binding pocket. (B) Model of eIF2B decamer assembly mediated by ISRIB. Top and side views of the same assembly path are shown (11). (C) Model of the eIF2B•eIF2αβγ complex. The interaction stabilizes the open conformation of eIF2γ’s GTP binding site, thus catalyzing GTP exchange. (D) Model of eIF2B bound to its inhibitor eIF2-P. eIF2-P binds to a different site on eIF2B, noncompetitively blocking eIF2B’s GEF activity. (E) Bell-shaped response of ISR inhibition by ISRIB. ISRIB blocks the ISR only at intermediate activation levels, as shown in (22).