The polypeptide tunnel system in the ribosome and its gating in erythromycin resistance mutants of L4 and L22

Variations in the inner ribosomal landscape determining the topology of nas cent protein transport have been studied by three-dimensional cryo-electron microscopy of erythromycin-resistant Escherichia coli 70S ribosomes. Signi ficant differences in the mouth of the 50S subunit tunnel system visualized in the present study support a simple steric-hindrance explanation for the action of the drug. Examination of ribosomes in different functional state s suggests that opening and closing of the main tunnel are dynamic features of the large subunit, possibly accompanied by changes in the L7/L12 stalk region. The existence and dynamic behavior of side tunnels suggest that rib osomal proteins L4 and L22 might be involved in the regulation of a multipl e exit system facilitating cotranslational processing (or folding or direct ing) of nascent proteins.