Bacterial 30S ribosomal subunit protein S12 (RpsL)

The Bacterial 30S ribosomal subunit protein S12 (RpsL) is an essential component of the small ribosomal subunit, located at the decoding center (A-site) where it facilitates the accurate selection of aminoacyl-tRNA during translation [UniProt P0A7S3]. It functions by stabilizing the 'closed' conformation of the 30S subunit, a structural transition required for the acceptance of cognate tRNA and the rejection of near-cognate species [PubMed: 11014182]. S12 is the primary target for streptomycin, which binds at the interface of S12 and the 16S rRNA (specifically helix 44), inducing conformational changes that lower the energy barrier for non-cognate tRNA binding, thereby causing mRNA misreading [PubMed: 10952312]. This protein is also involved in the mechanism of action for other aminoglycosides and tuberactinomycins like capreomycin, which disrupt protein synthesis by targeting the decoding site [PubMed: 15805515]. Mutations in the rpsL gene, such as the K42R substitution, are major drivers of high-level streptomycin resistance and can lead to a 'hyper-accurate' ribosomal state that significantly reduces translational speed [PubMed: 20606008].

Other names

30S ribosomal protein S12Small ribosomal subunit protein S12RpsLDecoding site protein S12Ribosomal protein S12

Aminoglycosides bind to the decoding site (A-site) of the 30S ribosomal subunit, specifically at the interface of the S12 protein and the 16S rRNA. This binding stabilizes the 'closed' conformation of the ribosome, which reduces the energy barrier for tRNA selection and leads to the incorporation of incorrect amino acids (misreading). It also interferes with the translocation of the mRNA-tRNA complex [PubMed: 10952312, 11014182].