Structure of a 30S Pre-initiation Complex Stalled by GE81112 Reveals Structural Parallels in Bacterial and Eukaryotic Protein Synthesis Initiation Pathways

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2016 Dec 18

PMID 27986852

Citations 18

Authors

Jorge P Lopez-Alonso

Attilio Fabbretti

Tatsuya Kaminishi

Idoia Iturrioz

Letizia Brandi

David Gil-Carton

Claudio O Gualerzi

Paola Fucini

Sean R Connell

Affiliations

Soon will be listed here.

Abstract

In bacteria, the start site and the reading frame of the messenger RNA are selected by the small ribosomal subunit (30S) when the start codon, typically an AUG, is decoded in the P-site by the initiator tRNA in a process guided and controlled by three initiation factors. This process can be efficiently inhibited by GE81112, a natural tetrapeptide antibiotic that is highly specific toward bacteria. Here GE81112 was used to stabilize the 30S pre-initiation complex and obtain its structure by cryo-electron microscopy. The results obtained reveal the occurrence of changes in both the ribosome conformation and initiator tRNA position that may play a critical role in controlling translational fidelity. Furthermore, the structure highlights similarities with the early steps of initiation in eukaryotes suggesting that shared structural features guide initiation in all kingdoms of life.

Citing Articles

The translation inhibitors kasugamycin, edeine and GE81112 target distinct steps during 30S initiation complex formation.

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A binding site for the antibiotic GE81112 in the ribosomal mRNA channel.

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