eIF2

Once the initiation phase has completed, eIF2 is released from the ribosome bound to GDP as an inactive binary complex.

eIF2 is an essential factor for protein synthesis that forms a ternary complex (TC) with GTP and the initiator Met-tRNAiMet.

After its formation, the TC binds the 40S ribosomal subunit to form the 43S preinitiation complex (43S PIC).

43S PIC assembly is believed to be stimulated by the initiation factors eIF1, eIF1A, and the eIF3 complex according to in vitro experiments.

Upon base pairing of the AUG-codon with the Met-tRNA, eIF5 (which is a GTPase-activating protein, or GAP) is recruited to the complex and induces eIF2 to hydrolyse its GTP.

Since the cellular concentration of eIF2B is much lower than that of eIF2, even a small amount of phosphorylated eIF2 can completely abolish eIF2B activity by sequestration.

Furthermore, low concentration of ternary complex allows the expression of GCN4 (starved condition), which, in turn, results in increased activation of amino acid synthesis genes[2][3][4][9][11] Since eIF2 is essential for most forms of translation initiation and therefore protein synthesis, defects in eIF2 are often lethal.

The protein is highly conserved among evolutionary remote species - indicating a large impact of mutations on cell viability.

Potentially reduced levels of unstable regulatory proteins might play a role in the development of the diseases mentioned.

Mode of action of eRF, an eIF-2-recycling factor from rabbit reticulocytes involved in GDP/GTP exchange.