Initiation of Protein Synthesis

This chapter contains sections titled: Initiation of Protein Synthesis in Eubacteria Overview of Initiation in Eubacteria Specialized initiation events: translational coupling, 70S initiation and leaderless mRNAs Initiation Factor 1 Binds to the Ribosomal A-site The Domain Structure of Bacterial IF2 Interaction Partners of IF2 The Role of the IF2-dependent GTPase Activity The Mystery of the IF3-binding Site on the 30S Subunit References Mechanism and Regulation of Protein Synthesis Initiation in Eukaryotes Introduction Overview of Translation-initiation Pathways in Eukaryotes and Prokaryotes Conservation and diversity of translation-initiation factors among bacteria, archaea and eukaryotes Genetic assays for in vivo functions of eIF2 Generation of Free 40S Subunits and 40S Binding of Met-tRNA Dissociation of Idle 80S Ribosomes Components of the eIF2/GTP/Met-tRNA Ternary Complex The GEF eIF2B regulates ternary complex formation Binding of Ternary Complex and mRNA to the 40S Ribosome is Stimulated by eIF3 eIF1A Stimulates Ternary Complex Binding to 40S Subunits and Participates in AUG Selection During Scanning Binding of Ribosomes to mRNA The Ends of Eukaryotic mRNAs Contain Distinctive Conserved Structures Ribosome Binding to mRNA is Stimulated by the eIF4 Factors Circularization of mRNA via eIF4G–PABP Interaction Translational Control by mRNA Circularization Regulation of eIF4 Function by Phosphorylation eIF4E Phosphorylation eIF4E-4E-BPs eIF4G Phosphorylation eIF4B Phosphorylation Translational Control by Paips – PABP Interacting Proteins AUG Recognition during Scanning AUG is the Predominant Signal for Initiation and is Selected by Proximity to the 59-end by the Scanning Mechanism The Anticodon of tRNA, eIF2 Subunits, eIF1, and eIF5 are Determinants of AUG Selection during Scanning eIF1 plays a role in TC binding, scanning, and AUG selection eIF5 Functions as a GTPase Activating Protein for eIF2 in AUG Selection and Subunit Joining Joining of 60S Subunits to 40S Ribosomal Complexes eIF5B Catalyzes a Second GTP-dependent Step in Translation Initiation GTPase Switch Regulates Ribosome Affinity of eIF5B and Governs Translational Efficiency IRES-mediated Translation Initiation Future Prospects References