eIF2GTPtRNAiMet

eIF2GTPtRNAiMet is the eukaryotic initiation factor 2 ternary complex comprising the GTP-bound form of eIF2 bound to the initiator methionyl-tRNA (tRNAiMet). This complex delivers Met-tRNAiMet to the 40S ribosomal subunit during the start of translation, enabling recognition of the start codon in conjunction with other initiation factors.

Formation and regulation: In its active state, eIF2 binds GTP and tRNAiMet to form the ternary complex. GDP-bound eIF2 is recycled to the GTP-bound form by the guanine nucleotide exchange factor eIF2B, a step that can limit initiation rate. Phosphorylation of the eIF2α subunit (on Ser51) by stress-activated kinases reduces GDP–GTP exchange, thereby lowering levels of eIF2-GTP-tRNAiMet and global translation initiation during cellular stress.

Mechanism: The ternary complex associates with the 40S ribosomal subunit in the 43S pre-initiation complex along with eIF1, eIF1A, eIF3, and eIF5. Following mRNA loading and scanning for AUG, start codon recognition promotes GTP hydrolysis on eIF2, catalyzed by eIF5. This converts eIF2-GTP to eIF2-GDP and leads to release of eIF2-GDP from the ribosome. Recycled eIF2, via eIF2B, can reform the ternary complex to initiate a new round of translation.

In eukaryotes, tRNAiMet is the initiator methionine tRNA and is not formylated as in bacteria; its charging and delivery are tightly coupled to translation initiation through eIF2-dependent mechanisms.