title: 2.8-Å Cryo-EM Structure of the Large Ribosomal Subunit from the Eukaryotic Parasite Leishmania.
abstract: Leishmania is a single-cell eukaryotic parasite of the Trypanosomatidae family, whose members cause an array of tropical diseases. The often fatal outcome of infections, lack of effective vaccines, limited selection of therapeutic drugs, and emerging resistant strains, underline the need to develop strategies to combat these pathogens. The Trypanosomatid ribosome has recently been highlighted as a promising therapeutic target due to structural features that are distinct from other eukaryotes. Here, we present the 2.8-Å resolution structure of the Leishmania donovani large ribosomal subunit (LSU) derived from a cryo-EM map, further enabling the structural observation of eukaryotic rRNA modifications that play a significant role in ribosome assembly and function. The structure illustrates the unique fragmented nature of leishmanial LSU rRNA and highlights the irregular distribution of rRNA modifications in Leishmania, a characteristic with implications for anti-parasitic drug development.
authors.affiliation: Department of Structural Biology, Faculty of Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Moran
authors.initials: M
authors.lastname: Shalev-Benami
authors.affiliation: Life Sciences Institute and Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Structural Biology, Faculty of Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Donna
authors.initials: D
authors.lastname: Matzov
authors.affiliation: Department of Structural Biology, Faculty of Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Halfon
authors.affiliation: Department of Microbiology and Molecular Genetics, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem 9112102, Israel.
authors.forename: Arie
authors.initials: A
authors.lastname: Zackay
authors.affiliation: Department of Structural Biology, Faculty of Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Haim
authors.initials: H
authors.lastname: Rozenberg
authors.affiliation: Department of Structural Biology, Faculty of Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Ella
authors.initials: E
authors.lastname: Zimmerman
authors.affiliation: Department of Structural Biology, Faculty of Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Bashan
authors.affiliation: Department of Microbiology and Molecular Genetics, IMRIC, Hebrew University-Hadassah Medical School, Jerusalem 9112102, Israel.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Jaffe
authors.affiliation: Department of Structural Biology, Faculty of Chemistry, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: ada.yonath@weizmann.ac.il.
authors.forename: Ada
authors.initials: A
authors.lastname: Yonath
authors.affiliation: Life Sciences Institute and Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: skinioti@umich.edu.
authors.forename: Georgios
authors.initials: G
authors.lastname: Skiniotis
mesh_terms: D020285:Cryoelectron Microscopy; D007893:Leishmania donovani; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D020836:Protein Structure, Quaternary; D015800:Protozoan Proteins / Q000737:chemistry; D016053:RNA, Protozoan / Q000737:chemistry; D012335:RNA, Ribosomal / Q000737:chemistry; D012269:Ribosomal Proteins / Q000737:chemistry; D054658:Ribosome Subunits, Large / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D015800:Protozoan Proteins; D016053:RNA, Protozoan; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins