The crystal structure of ribosomal protein L22 from Thermus thermophilus: insights into the mechanism of erythromycin resistance

Background: The ribosomal protein L22 is one of five proteins necessary for the formation of an early folding intermediate of the 23S rRNA. L22 has be en found on the cytoplasmic side of the 50S ribosomal subunit. It can also be labeled by an erythromycin derivative bound close to the peptidyl-transf er center at the interlace side of the 50S subunit, and the amino acid sequ ence of an erythromycin-resistant mutant is known. Knowing the structure of the protein may resolve this apparent conflict regarding the location of L 22 on the ribosome. Results: The structure of Thermus thermophilus L22 was solved using X-ray c rystallography, L22 consists of a small alpha+beta domain and a protruding beta hairpin that is 30 Angstrom long. A large part of the surface area of the protein has the potential to be involved in interactions with rRNA, A s tructural similarity to other RNA-binding proteins is found, possibly indic ating a common evolutionary origin. Conclusions: The extensive surface area of L22 has the characteristics of a n RNA-binding protein, consistent with its role in the folding of the 23S r RNA. The erythromycin resistance conferring mutation is located in the prot ruding beta hairpin that is postulated to be important in L22-rRNA interact ions. This region of the protein might be at the erythromycin-binding site close to the peptidyl transferase center, whereas the opposite end may be e xposed to the cytoplasm.