48S

48S refers to a ribosomal pre-initiation complex in eukaryotic translation initiation. It forms during the initiation phase when the small ribosomal subunit (40S) associates with initiator tRNA and messenger RNA in the presence of several initiation factors. The 48S particle contains the 40S subunit, Met-tRNAiMet, the mRNA, and initiation factors such as eIF2 bound to GTP (the ternary complex), eIF3, eIF1, eIF1A, and the eIF4F cap-binding complex (comprising eIF4E, eIF4G, and eIF4A). The mRNA is recruited to the 40S subunit with the help of eIF4F and other factors, forming the 48S initiation complex. The 48S particle then scans the 5' untranslated region for an AUG start codon. When the start codon is recognized by the anticodon of Met-tRNAiMet, GTP hydrolysis occurs on eIF2, initiation factors are released, and the 60S ribosomal subunit joins to form the 80S initiation complex, allowing elongation to begin. The 48S state has been visualized by cryo-electron microscopy and is central to start-site selection and translational control. Regulation of 48S formation and start codon recognition is influenced by signaling pathways that modulate eIF2 activity (for example, eIF2α phosphorylation) and the assembly of the eIF4F complex (such as 4E-BP–mediated control). Disruptions in 48S formation can affect protein synthesis and are relevant in stress responses and disease.