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Albany 2013: Book of Abstracts

category image Albany 2013
Conversation 18
June 11-15 2013
©Adenine Press (2012)

High-resolution cryo-electron microscopy structure of the Trypanosoma brucei ribosome

Ribosomes, the protein factories of living cells, translate genetic information carried by messenger RNAs into proteins, and are thus involved in virtually all aspects of cellular development and maintenance. The few available structures of the eukaryotic ribosome reveal that it is more complex than its prokaryotic counterpart, owing mainly to the presence of eukaryote-specific ribosomal proteins and additional ribosomal RNA insertions, called expansion segments. The structures also differ among species, partly in the size and arrangement of these expansion segments. Such differences are extreme in kinetoplastids. Here we present a high-resolution (~5┼) cryo-electron microscopy structure of the ribosome of Trypanosoma brucei, the parasite that is transmitted by the tsetse fly and that causes African Sleeping Sickness. The atomic model reveals the unique features of this ribosome, characterized mainly by the presence of unusually large eukaryotic expansion segments and ribosomal protein extensions leading to the formation of four additional inter-subunit bridges. We also find additional rRNA insertions, including one large rRNA domain that is not found in other eukaryotes. Furthermore, the structure reveals the five cleavage sites of the kinetoplastid large ribosomal subunit rRNA chain, which is known to be cleaved uniquely into six pieces, and suggests that the cleavage is important for the maintenance of the T. brucei ribosome in the observed structure. We discuss several possible implications of the large rRNA expansion segments for the translation regulation process, and we show a possible link between the protein translation initiation process and expansion segments 6 and 7 on the small ribosomal subunit. Our structure could serve as a basis for future experiments aimed at understanding the functional importance of these kinetoplastid-specific ribosomal features in protein translation regulation, an essential step towards finding effective and safe kinetoplastid-specific drugs.

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Reference

Hashem Y. et al., (2013). High-resolution cryo-electron microscopy structure of the Trypanosoma brucei ribosome. Nature 494, 385-389. doi:10.1038/nature11872.

Yaser Hashem1
Amedee des Georges1
Jie Fu2
Sarah N. Buss3
Fabrice Jossinet4
Amy Jobe 5
Qin Zhang6
Hstau Y. Liao2
Robert A. Grassucci1
Chandrajit Bajaj6
Eric Westhof4
Susan Madison-Antenucci3
Joachim Frank 1, 5

1 HHMI
Dept. of Biochemistry and Molecular Biophysics
650 W 168th St.
Columbia University
New York, NY 10032
2 Department of Biochemistry and Molecular Biophysics
Columbia University
New York
3 Wadsworth Center
Albany, New York
4 Institut de Biologie MolÚculaire et Cellulaire (CNRS)
Strasbourg 67084
France
5 Department of Biological Sciences
Columbia University
New York
6 Department of Computer Science
University of Texas
Austin, Texas

Ph: (212) 305-9510
Fx: (212) 305-9500
jf2192@columbia.edu