Structure of a 30S pre-initiation complex stalled by GE81112 reveals structural parallels in bacterial and eukaryotic protein synthesis initiation pathways
- Jorge P. López-Alonso1,
- Attilio Fabbretti2,
- Tatsuya Kaminishi1,
- Idoia Iturrioz1,
- Letizia Brandi2,
- David Gil-Carton1,
- Claudio O. Gualerzi2,*,
- Paola Fucini1,3 and
- Sean R. Connell 1 , 3 , *
- 1Structural Biology Unit, CIC bioGUNE, Parque Tecnológico de Bizkaia, 48160 Derio, Bizkaia, Spain
- 2Laboratory of Genetics, University of Camerino, 62032 Camerino, Italy
- 3IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain
- ↵*To whom correspondence should be addressed. Tel: +34 946 572 529; Email: sean.connell{at}gmail.com
- ↵Correspondence may also be addressed to Claudio O. Gualerzi. Tel: +39 0737 403240; Fax: +39 0737 403290; Email: claudio.gualerzi{at}unicam.it
- Received August 12, 2016.
- Revision received November 22, 2016.
- Accepted December 13, 2016.
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.
- © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
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