title: On peptide bond formation, translocation, nascent protein progression and the regulatory properties of ribosomes. Derived on 20 October 2002 at the 28th FEBS Meeting in Istanbul.
abstract: High-resolution crystal structures of large ribosomal subunits from Deinococcus radiodurans complexed with tRNA-mimics indicate that precise substrate positioning, mandatory for efficient protein biosynthesis with no further conformational rearrangements, is governed by remote interactions of the tRNA helical features. Based on the peptidyl transferase center (PTC) architecture, on the placement of tRNA mimics, and on the existence of a two-fold related region consisting of about 180 nucleotides of the 23S RNA, we proposed a unified mechanism integrating peptide bond formation, A-to-P site translocation, and the entrance of the nascent protein into its exit tunnel. This mechanism implies sovereign, albeit correlated, motions of the tRNA termini and includes a spiral rotation of the A-site tRNA-3' end around a local two-fold rotation axis, identified within the PTC. PTC features, ensuring the precise orientation required for the A-site nucleophilic attack on the P-site carbonyl-carbon, guide these motions. Solvent mediated hydrogen transfer appears to facilitate peptide bond formation in conjunction with the spiral rotation. The detection of similar two-fold symmetry-related regions in all known structures of the large ribosomal subunit, indicate the universality of this mechanism, and emphasizes the significance of the ribosomal template for the precise alignment of the substrates as well as for accurate and efficient translocation. The symmetry-related region may also be involved in regulatory tasks, such as signal transmission between the ribosomal features facilitating the entrance and the release of the tRNA molecules. The protein exit tunnel is an additional feature that has a role in cellular regulation. We showed by crystallographic methods that this tunnel is capable of undergoing conformational oscillations and correlated the tunnel mobility with sequence discrimination, gating and intracellular regulation.
authors.affiliation: Department of Structural Biology, The Weizmann Institute, Rehovot, Israel.
authors.forename: Ilana
authors.initials: I
authors.lastname: Agmon
authors.forename: Tamar
authors.initials: T
authors.lastname: Auerbach
authors.forename: David
authors.initials: D
authors.lastname: Baram
authors.forename: Heike
authors.initials: H
authors.lastname: Bartels
authors.forename: Anat
authors.initials: A
authors.lastname: Bashan
authors.forename: Rita
authors.initials: R
authors.lastname: Berisio
authors.forename: Paola
authors.initials: P
authors.lastname: Fucini
authors.forename: Harly A S
authors.initials: HA
authors.lastname: Hansen
authors.forename: Joerg
authors.initials: J
authors.lastname: Harms
authors.forename: Maggie
authors.initials: M
authors.lastname: Kessler
authors.forename: Moshe
authors.initials: M
authors.lastname: Peretz
authors.forename: Frank
authors.initials: F
authors.lastname: Schluenzen
authors.forename: Ada
authors.initials: A
authors.lastname: Yonath
authors.forename: Raz
authors.initials: R
authors.lastname: Zarivach
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D034301:Deinococcus / Q000378:metabolism; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D021381:Protein Transport; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D010455:Peptides; D012343:RNA, Transfer