X-ray Structure of Translation Initiation Factor eIF2γ: Implications for tRNA and eIF2α binding

Abstract

The x-ray structure of the γ-subunit of the heterotrimeric translation initiation factor eIF2 has been determined to 2.4-Å resolution. eIF2 is a GTPase that delivers the initiator Met-tRNA to the P site on the small ribosomal subunit during a rate-limiting initiation step in translation. The structure of eIF2γ closely resembles that of EF1A·GTP, consisting of an N-terminal G domain followed by two β-barrels arranged in a closed configuration with domain II packed against the G domain in the vicinity of the Switch regions. The G domain of eIF2γ has an unusual zinc ribbon motif, not previously found in other GTPases. Structure-based site-directed mutagenesis was used to identify two adjacent features on the surface of eIF2γ that bind the α-subunit and Met-tRNAiMet, respectively. These structural, biochemical, and genetic results provide new insights into eIF2 ternary complex assembly.