Ribosomal crystallography: initiation, peptide bond formation, and amino acid polymerization are hampered by antibiotics.
High-resolution structures of ribosomal complexes revealed that minute amounts of clinically relevant antibiotics hamper protein biosynthesis by limiting ribosomal mobility or perturbing its elaborate architecture, designed for navigating and controlling peptide bond formation and continuous amino acid polymerization. To accomplish this, the ribosome contributes positional rather than chemical catalysis, provides remote interactions governing accurate substrate alignment within the flexible peptidyl-transferase center (PTC) pocket, and ensures nascent-protein chirality through spatial limitations. Peptide bond formation is concurrent with aminoacylated-tRNA 3' end translocation and is performed by a rotatory motion around the axis of a sizable ribosomal symmetry-related region, which is located around the PTC in all known crystal structures. Guided by ribosomal-RNA scaffold along an exact pattern, the rotatory motion results in stereochemistry that is optimal for peptide bond formation and for nascent protein entrance into the exit tunnel, the main target of antibiotics targeting ribosomes. By connecting the PTC, the decoding center, and the tRNA entrance and exit regions, the symmetry-related region can transfer intraribosomal signals, guaranteeing smooth processivity of amino acid polymerization.
Yonath
Ada
A
Department of Structural Biology, The Weizmann Institute, 76100 Rehovot, Israel. ada.yonath@weizmann.ac.il
Bashan
Anat
A
D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D010458:Peptidyl Transferases / Q000737:chemistry / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism*; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism*
D000596:Amino Acids; D000900:Anti-Bacterial Agents; D012333:RNA, Messenger; D012343:RNA, Transfer; D010458:Peptidyl Transferases