Structural Studies of the Functional Complexes of the 50S and 70S Ribosome, a Major Antibiotic Target

摘要

Our crystal structure of the Haloarcula marismortui (H.ma.) 50S ribosomal subunit and its complexes with substrates and antibiotics have illuminated the mechanism of peptide bond formation and its inhibition by antibiotics. Our structures of the Thermus thermophilus (T.th.) 70S ribosome complexed with tRNAs, protein factor EF-P or antibiotics have also provided insights into their mechanisms of action. We conclude that the CCA ends of the A- and P-site tRNAs bind to the 70S ribosome as the CCA fragments bind to the 50S subunit; macrolide antibiotics bind to the T.th. 70S ribosome as they bind to the H.ma. 50S subunit; EF-P binds to the 70S ribosome adjacent to and interacting with a P-site tRNA, and cryoEM maps of a 70S ribosome bound to a peptidyl-tRNA containing an arresting sequence shows an extended polypeptide interacting with the tunnel wall.