4 research departments
750 employees
45 nationalities
55 research teams
16 ERC laureates
260 publications per year
24000 m² lab area

Support us through

Fondation universite de Strasbourg

Communication Service

Tél. +33(0) 3 88 65 35 47

Quick Links

Science & society

Key figures 2017

12 prizes and distinctions
3 public events
26 major scientific news

Scientific news

Integrated approach in structural biology: initiation factor IF2 from every angle

3D visualization of the entire IF2 factor (left) and its stabilization role of transfer RNA (red) on the small subunit of the ribosome (30S in yellow). On the left, the N-terminal domain (blue helix) is present. Its removal (right) leads to a bad positioning of IF2 and tRNA, thus blocking the joining of the ribosome subunits (30S and 50S).

Initiation factor 2 crystal structure reveals a different domain organization from eukaryotic initiation factor 5B and mechanism among translational GTPases.

Eiler D, Lin J, Simonetti A, Klaholz BP, Steitz TA.

Proc Natl Acad Sci U S A Sept. 24, 2013

Involvement of protein IF2 N domain in ribosomal subunit joining revealed from architecture and function of the full-length initiation factor.

Simonetti A, Marzi S, Billas IM, Tsai A, Fabbretti A, Myasnikov AG, Roblin P, Vaiana AC, Hazemann I, Eiler D, Steitz TA, Puglisi JD, Gualerzi CO, Klaholz BP.

Proc Natl Acad Sci U S A Sept. 24, 2013

Sept. 24, 2013

DNA transcription into mRNA, mRNA recognition, mRNA translation, the protein synthesis involves many molecules, the complex mechanisms of which are far from been all elucidated… Bruno Klaholz’s team got interested in the translation factor IF2 which participates in translation initiation in bacteria. Combining many technologies in structural biology, researchers succeeded in describing with precision this molecule. They notably brought to light a domain of its structure particularly important for the assembly mechanisms of the ribosome subunits, unveiling a very different functioning from its eukaryote counterpart. These results have been published on September 24th in Proceedings of the National Academy of Sciences.

IF2 role in mRNA translation
Protein synthesis is a basic process of the biochemistry of life. Permanently, our DNA is transcribed in messenger RNA, itself translated into proteins. The latter step is very complex and involves many regulatory proteins, especially during the initiation process which is highly regulated on the ribosome. Ribosomes are the “molecular machineries” that carry out the mRNA reading and the synthesis of the corresponding proteins. This macromolecule interacts with many others, notably during its assembly. In bacteria, the joining of the two ribosome subunits is promoted by initiation factor IF2. Researchers have focused on the structure of this molecule in order to better understand the initiation mechanism of translation.


Decyphering IF2 structure
IF2 is a multidomain protein (see figure). Bruno Klaholz’s team had already tried to crystallize it, but only managed to observe the enzymatic part of the molecule, as the rest got removed during experiments. Combining results from crystallography, small-angle X-ray scattering (SAXS) and cryo electron microscopy, researchers have now achieved to determine the entire 3D structure of IF2, both in solution and in its state bound to the ribosome, in which it stabilizes the initiator transfer RNA that carries the first amino acid of the future protein to be synthetized. Then they launched into the functional analysis of IF2 by fast kinetics and single molecule fluorescence (in collaboration with the teams of Claudio Gualerzi, Camerino, and Jody Puglisi, Stanford), analyzing dynamics of the complex with in presence and absence of the N-terminal domain, and showing its crucial role in the formation of a ribosome ready for beginning protein synthesis. Notably, they observed that its absence causes a bad assembly of the ribosome and therefore obstruct its activity.

In this study, Bruno Klaholz’s team also set up a collaboration with Thomas Steitz’s team from Yale University (USA), that enabled them to exchange their results on the IF2 structure and to create a synergy for the study of the entire factor. The scientists then showed in a second article* published in the same PNAS issue that the mechanism of ribosome assembly catalyzed by the N-terminal extremity of IF2 is rather different from the one known for its eukaryote counterpart, eIF5B. These results are providing key information about the molecular mechanism of translation initiation, a decisive step for the regulation of protein synthesis.

Imprimer Envoyer

Université de Strasbourg

IGBMC - CNRS UMR 7104 - Inserm U 1258
1 rue Laurent Fries / BP 10142 / 67404 Illkirch CEDEX / France Tél +33 (0)3 88 65 32 00 / Fax +33 (0)3 88 65 32 01 / directeur.igbmc@igbmc.fr