The Department of Biomedicine

BBB Seminar: Marat Yusupov

X-ray ribosome structure. Localization of mRNA and tRNAs on the ribosome

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Marat Yusupov
Laboratoire de Biologie et Genomiques Structurales du CNRS, IGBMC, Illkirch CEDEX-CU de Strasbourg, France

We have solved the crystal structure of the complete Thermus thermophilus 70S ribosome containing bound mRNA and tRNAs at 5.5 Å resolution. All of the 16S, 23S and 5S rRNA chains, the A-, P-and E-site tRNAs, mRNA and all ribosomal proteins have been fitted to the electron density map. The core of the interface between the 30S small subunit and the 50S large subunit, where the tRNA substrates are bound, is dominated by RNA, with proteins located mainly at the periphery, consistent with ribosomal function being based on rRNA. In each of the three tRNA binding sites, the ribosome contacts all of the major elements of tRNA, providing an explanation for the conservation of tRNA structure. The tRNAs are closely juxtaposed with the intersubunit bridges, in way that suggests coupling of the 20 to 50 Å movements associated with tRNA translocation with intersubunit movement. About 30 nucleotides of the mRNA are wrapped in the groove that encircles the neck of the 30S subunit. The Shine-Dalgarno helix is bound in a large cleft between the head and the platform. Only about eight nucleotides, centred on the junction between the A and P codons, are exposed on the interface of the 30S subunit.

Key references:
Yusupov M et al. (2001) Crystal structure of the ribosome at 5.5 Å resolution. Science 292, 883-896.
Yusupova G et al. (2001) The path of messenger RNA through the ribosome. Cell 106, 233-241.

Dr. Marat Yusupov began his structural studies on the ribosome in the mid 1980ies at the Institute of Protein Research, Academy of Sciences in Puschino, Moscow Region, USSR. In the early 90ies the research opportunities in Russia were drastically reduced and Marat Yusupov and his collaborating wife Gullara Yusupova left for France where they were able to continue their structural studies at the CNRS (Centre National de la Recherche Scientifique), Unite Structure des Macromolecules Biologiques et Mecanismes de Reconnaissance, in Illkirch outside of Strasbourg. A few years later the Yusupovs moved again, this time to the Center for Molecular Biology of RNA, Sinsheimer Laboratories, University of California at Santa Cruz, USA. It was here that Marat Yusupov with his wife and colleagues in the group of Harry Noller published in 2001 the first molecular view of a complex bacterial ribosome, describing its structure down to the 5,5 Å level. This discovery made the front page of the Science magazine and, furthermore, landed the Yusupovs the AAAS Newcomb Cleveland Prize 2001 for their outstanding paper. Since autumn 2001 the Yusupovs are back in France at the CNRS from where they now together with their colleagues pursue the resolution of the ribosomal structure down towards the molecular level.