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Proc Natl Acad Sci U S A. 2016 Oct 25;113(43):12174-12179. Epub 2016 Oct 10.

Structure and assembly model for the Trypanosoma cruzi 60S ribosomal subunit.

Author information

1
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032.
2
Department of Biological Sciences, Columbia University, New York, NY 10027.
3
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032; Howard Hughes Medical Institute, Columbia University, New York, NY 10027.
4
Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213.
5
Parasitology Laboratory, Wadsworth Center, New York State Department of Health, Albany, NY 12208.
6
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032; Department of Biological Sciences, Columbia University, New York, NY 10027; Howard Hughes Medical Institute, Columbia University, New York, NY 10027; jf2192@cumc.columbia.edu.

Abstract

Ribosomes of trypanosomatids, a family of protozoan parasites causing debilitating human diseases, possess multiply fragmented rRNAs that together are analogous to 28S rRNA, unusually large rRNA expansion segments, and r-protein variations compared with other eukaryotic ribosomes. To investigate the architecture of the trypanosomatid ribosomes, we determined the 2.5-Å structure of the Trypanosoma cruzi ribosome large subunit by single-particle cryo-EM. Examination of this structure and comparative analysis of the yeast ribosomal assembly pathway allowed us to develop a stepwise assembly model for the eight pieces of the large subunit rRNAs and a number of ancillary "glue" proteins. This model can be applied to the characterization of Trypanosoma brucei and Leishmania spp. ribosomes as well. Together with other details, our atomic-level structure may provide a foundation for structure-based design of antitrypanosome drugs.

KEYWORDS:

Trypanosoma cruzi; antitrypanosome drug design; biogenesis; multiply fragmented rRNA; ribosome structure

PMID:
27791004
PMCID:
PMC5087005
DOI:
10.1073/pnas.1614594113
[Indexed for MEDLINE]
Free PMC Article

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