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Molecular architecture of 40S translation initiation complexes on the hepatitis C virus IRES.

EMBO J. 2022-08; 
Zuben P Brown , Irina S Abaeva , Swastik De , Christopher U T Hellen , Tatyana V Pestova , Joachim Frank
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Gene Synthesis A derivative for transcription of HCV IRES lacking domain II (containing HCV nt. 125–375) was made by GenScript Corp. Get A Quote

Abstract

Hepatitis C virus mRNA contains an internal ribosome entry site (IRES) that mediates end-independent translation initiation, requiring a subset of eukaryotic initiation factors (eIFs). Biochemical studies revealed that direct binding of the IRES to the 40S ribosomal subunit places the initiation codon into the P site, where it base pairs with eIF2-bound Met-tRNAiMet forming a 48S initiation complex. Subsequently, eIF5 and eIF5B mediate subunit joining, yielding an elongation-competent 80S ribosome. Initiation can also proceed without eIF2, in which case Met-tRNAiMet is recruited directly by eIF5B. However, the structures of initiation complexes assembled on the HCV IRES, the transitions between different states... More

Keywords

eIF2; eIF5B; hepatitis C virus IRES; ribosome; translation initiation.