title: Ribosomal crystallography: peptide bond formation and its inhibition.
abstract: Ribosomes, the universal cellular organelles catalyzing the translation of genetic code into proteins, are protein/RNA assemblies, of a molecular weight 2.5 mega Daltons or higher. They are built of two subunits that associate for performing protein biosynthesis. The large subunit creates the peptide bond and provides the path for emerging proteins. The small has key roles in initiating the process and controlling its fidelity. Crystallographic studies on complexes of the small and the large eubacterial ribosomal subunits with substrate analogs, antibiotics, and inhibitors confirmed that the ribosomal RNA governs most of its activities, and indicated that the main catalytic contribution of the ribosome is the precise positioning and alignment of its substrates, the tRNA molecules. A symmetry-related region of a significant size, containing about two hundred nucleotides, was revealed in all known structures of the large ribosomal subunit, despite the asymmetric nature of the ribosome. The symmetry rotation axis, identified in the middle of the peptide-bond formation site, coincides with the bond connecting the tRNA double-helical features with its single-stranded 3' end, which is the moiety carrying the amino acids. This thus implies sovereign movements of tRNA features and suggests that tRNA translocation involves a rotatory motion within the ribosomal active site. This motion is guided and anchored by ribosomal nucleotides belonging to the active site walls, and results in geometry suitable for peptide-bond formation with no significant rearrangements. The sole geometrical requirement for this proposed mechanism is that the initial P-site tRNA adopts the flipped orientation. The rotatory motion is the major component of unified machinery for peptide-bond formation, translocation, and nascent protein progression, since its spiral nature ensures the entrance of the nascent peptide into the ribosomal exit tunnel. This tunnel, assumed to be a passive path for the growing chains, was found to be involved dynamically in gating and discrimination.
authors.affiliation: Department of Structural Biology, The Weizmann Institute, 76100 Rehovot, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Bashan
authors.forename: Raz
authors.initials: R
authors.lastname: Zarivach
authors.forename: Frank
authors.initials: F
authors.lastname: Schluenzen
authors.forename: Ilana
authors.initials: I
authors.lastname: Agmon
authors.forename: Joerg
authors.initials: J
authors.lastname: Harms
authors.forename: Tamar
authors.initials: T
authors.lastname: Auerbach
authors.forename: David
authors.initials: D
authors.lastname: Baram
authors.forename: Rita
authors.initials: R
authors.lastname: Berisio
authors.forename: Heike
authors.initials: H
authors.lastname: Bartels
authors.forename: Harly A S
authors.initials: HA
authors.lastname: Hansen
authors.forename: Paola
authors.initials: P
authors.lastname: Fucini
authors.forename: Daniel
authors.initials: D
authors.lastname: Wilson
authors.forename: Moshe
authors.initials: M
authors.lastname: Peretz
authors.forename: Maggie
authors.initials: M
authors.lastname: Kessler
authors.forename: Ada
authors.initials: A
authors.lastname: Yonath
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry; D020134:Catalytic Domain; D018360:Crystallography, X-Ray / Q000379:methods*; D008958:Models, Molecular; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D010455:Peptides / Q000737:chemistry; D010458:Peptidyl Transferases / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D012313:RNA / Q000737:chemistry; D012343:RNA, Transfer / Q000737:chemistry; D012270:Ribosomes / Q000737:chemistry*; D013752:Tetracycline / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D012313:RNA; D012343:RNA, Transfer; D010458:Peptidyl Transferases; D013752:Tetracycline