Inhibition of the recycling of eIF2 by HRI during translational initiation. eIF2 is a heterotrimeric protein with GTP/GDP-binding site on the γ-subunit. In the initiation of translation, active eIF2-GTP binds initiating methionyl-tRNA and 40S ribosomal subunit to form 43S preinitiation complex. Upon the joining of the 60S ribosomal subunit, GTP bound to eIF2 is hydrolyzed to GDP as an energy source for the joining reaction to form 80S initiating ribosome. To recycle eIF2 for another round of initiation, it is necessary to exchange the bound GDP for GTP. This exchange reaction is catalyzed by another initiation factor eIF2B, which is present in a limiting amount. When eIF2 is phosphorylated by HRI on the Ser51 of the α-subunit, it binds to eIF2B tightly and inactivates eIF2B activity. Depletion of functional eIF2B, therefore, keeps eIF-2 strained in the inactive GDP state and inhibits protein synthesis.