Importance of tRNA interactions with 23S rRNA for peptide bond formation on the ribosome: studies with substrate analogs.

Abstract:

:The major enzymatic activity of the ribosome is the catalysis of peptide bond formation. The active site -- the peptidyl transferase center -- is composed of ribosomal RNA (rRNA), and interactions between rRNA and the reactants, peptidyl-tRNA and aminoacyl-tRNA, are crucial for the reaction to proceed rapidly and efficiently. Here, we describe the influence of rRNA interactions with cytidine residues in A-site substrate analogs (C-puromycin or CC-puromycin), mimicking C74 and C75 of tRNA on the reaction. Base-pairing of C75 with G2553 of 23S rRNA accelerates peptide bond formation, presumably by stabilizing the peptidyl transferase center in its productive conformation. When C74 is also present in the substrate analog, the reaction is slowed down considerably, indicating a slow step in substrate binding to the active site, which limits the reaction rate. The tRNA-rRNA interactions lead to a robust reaction that is insensitive to pH changes or base substitutions in 23S rRNA at the active site of the ribosome.

journal_name

Biol Chem

journal_title

Biological chemistry

authors

Beringer M,Rodnina MV

doi

10.1515/BC.2007.077

subject

Has Abstract

pub_date

2007-07-01 00:00:00

pages

687-91

issue

7

eissn

1431-6730

issn

1437-4315

journal_volume

388

pub_type

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