The initiation of mammalian protein synthesis and the mechanism of scanning

During translation initiation in eukaryotes, the small ribosomal subunit binds mRNA at the 5′-end and scans in the 5′ to 3′ direction to locate the initiation codon, form the 80S initiation complex and start the protein synthesis. This simple, yet intricate, process is guided by multiple initiation factors. We determined the structures of three complexes of the small ribosomal subunit that represent distinct steps in mammalian translation initiation. These structures reveal the locations of eIF1, eIF1A, mRNA and initiator tRNA bound to the small ribosomal subunit and provide insights into the details of translation initiation specific to eukaryotes. Conformational changes associated with the captured functional states reveal the dynamics of the interactions in the P site of the ribosome. These results have functional implications for the mechanism of mRNA scanning.