title: The Proto-Ribosome: an ancient nano-machine for peptide bond formation.
abstract: The ribosome is a ribozyme whose active site, the peptidyl transferase center (PTC) is situated within a highly conserved universal symmetrical region that connects all ribosomal functional centers involved in amino-acid polymerization. The linkage between this elaborate architecture and A-site tRNA position revealed that the A to P-site passage of the tRNA 3' terminus during protein synthesis is performed by a rotary motion, synchronized with the overall tRNA/mRNA sideways movement and Guided by the PTC. This rotary motion leads to suitable stereochemistry for peptide bond formation as well as for substrate mediated catalysis. Analysis of the substrate binding modes to ribosomes led to the hypothesis that the ancient ribosome produced single peptide bonds and non-coded chains, potentially in a similar manner to the modern PTC. Later in evolution, a mechanism, enabling some type of decoding genetic control triggered the emergence of the small ribosomal subunit or part of it. This seems to be the result of the appearance of reaction products that could have evolved after polypeptides capable of enzymatic function were generated sporadically, while an ancient stable RNA fold was converted into an old version of a tRNA molecule. As in the contemporary ribosome the symmetry relates only the backbone fold and nucleotides orientations but not nucleotide sequences, it emphasizes the superiority of functional requirement over sequence conservation, and indicates that the PTC may have evolved by gene fusion or gene duplication.
authors.affiliation: Department of Structural Biology, Weizmann Inst., 76100 Rehovot, Israel.
authors.forename: Chen
authors.initials: C
authors.lastname: Davidovich
authors.affiliation: Department of Structural Biology, Weizmann Inst., 76100 Rehovot, Israel.
authors.forename: Matthew
authors.initials: M
authors.lastname: Belousoff
authors.affiliation: Department of Structural Biology, Weizmann Inst., 76100 Rehovot, Israel.
authors.forename: Itai
authors.initials: I
authors.lastname: Wekselman
authors.affiliation: Department of Structural Biology, Weizmann Inst., 76100 Rehovot, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Shapira
authors.affiliation: Department of Structural Biology, Weizmann Inst., 76100 Rehovot, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Krupkin
authors.affiliation: Department of Structural Biology, Weizmann Inst., 76100 Rehovot, Israel.
authors.forename: Ella
authors.initials: E
authors.lastname: Zimmerman
authors.affiliation: Department of Structural Biology, Weizmann Inst., 76100 Rehovot, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Bashan
authors.affiliation: Department of Structural Biology, Weizmann Inst., 76100 Rehovot, Israel.
authors.forename: Ada
authors.initials: A
authors.lastname: Yonath
keywords: RNA world; evolving ribosomes; peptide bond formation; polymerase; ribozyme