Solving the Structure of eIF2 Bound to eIF2B Using Cryogenic Electron Microscopy
Translation begins when initiation factor-2 (eIF2) delivers methionyl initiator tRNA (Met-tRNAi) to the ribosome. The exchange of GDP bound to eIF2 for GTP is a prerequisite to binding Met-tRNAi and is mediated by a second initiation factor, eIF2B. Regulation of mRNA translation is achieved through phosphorylation of eIF2 α at Ser51 which converts eIF2 from a substrate into a competitive inhibitor of eIF2B. Using the latest cryo-electron microscopy (cryoEM) technologies in both collection and data processing we were able to obtain three high resolution structures to interrogate the structural basis of the integrated stress response.