title: Structure and assembly model for the Trypanosoma cruzi 60S ribosomal subunit.
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.
authors: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032.
authors: Zheng
authors: Z
authors: Liu
authors: Department of Biological Sciences, Columbia University, New York, NY 10027.
authors: Cristina
authors: C
authors: Gutierrez-Vargas
authors: Department of Biological Sciences, Columbia University, New York, NY 10027.
authors: Jia
authors: J
authors: Wei
authors: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032; Howard Hughes Medical Institute, Columbia University, New York, NY 10027.
authors: Robert A
authors: RA
authors: Grassucci
authors: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213.
authors: Madhumitha
authors: M
authors: Ramesh
authors: Parasitology Laboratory, Wadsworth Center, New York State Department of Health, Albany, NY 12208.
authors: Noel
authors: N
authors: Espina
authors: Department of Biological Sciences, Columbia University, New York, NY 10027.
authors: Ming
authors: M
authors: Sun
authors: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213.
authors: Beril
authors: B
authors: Tutuncuoglu
authors: Parasitology Laboratory, Wadsworth Center, New York State Department of Health, Albany, NY 12208.
authors: Susan
authors: S
authors: Madison-Antenucci
authors: Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213.
authors: John L
authors: JL
authors: Woolford
authors: Department of Biological Sciences, Columbia University, New York, NY 10027.
authors: Liang
authors: L
authors: Tong
authors: 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.
authors: Joachim
authors: J
authors: Frank
mesh_terms: D014355:Chagas Disease / Q000188:drug therapy / Q000469:parasitology; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D006801:Humans; D012335:RNA, Ribosomal / Q000235:genetics / Q000648:ultrastructure; D012269:Ribosomal Proteins / Q000737:chemistry / Q000235:genetics; D054683:Ribosome Subunits, Large, Eukaryotic / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure*; D012270:Ribosomes / Q000235:genetics / Q000648:ultrastructure*; D014349:Trypanosoma cruzi / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure
chemical_list: D012335:RNA, Ribosomal; D012269:Ribosomal Proteins
keywords: Trypanosoma cruzi; antitrypanosome drug design; biogenesis; multiply fragmented rRNA; ribosome structure