title: Structures and stabilization of kinetoplastid-specific split rRNAs revealed by comparing leishmanial and human ribosomes.
abstract: The recent success in ribosome structure determination by cryoEM has opened the door to defining structural differences between ribosomes of pathogenic organisms and humans and to understand ribosome-targeting antibiotics. Here, by direct electron-counting cryoEM, we have determined the structures of the Leishmania donovani and human ribosomes at 2.9 Å and 3.6 Å, respectively. Our structure of the leishmanial ribosome elucidates the organization of the six fragments of its large subunit rRNA (as opposed to a single 28S rRNA in most eukaryotes, including humans) and reveals atomic details of a unique 20 amino acid extension of the uL13 protein that pins down the ends of three of the rRNA fragments. The structure also fashions many large rRNA expansion segments. Direct comparison of our human and leishmanial ribosome structures at the decoding A-site sheds light on how the bacterial ribosome-targeting drug paromomycin selectively inhibits the eukaryotic L. donovani, but not human, ribosome.
authors.affiliation: Center of Cryo Electron Microscopy, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.|California NanoSystems Institute, University of California, Los Angeles, California 90095, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
authors.forename: Mason
authors.initials: M
authors.lastname: Lai
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
authors.forename: Winston
authors.initials: W
authors.lastname: Chang
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
authors.forename: Iris
authors.initials: I
authors.lastname: Yu
authors.affiliation: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Ding
authors.affiliation: Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Mrazek
authors.affiliation: Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Hwee L
authors.initials: HL
authors.lastname: Ng
authors.affiliation: California NanoSystems Institute, University of California, Los Angeles, California 90095, USA.|Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.affiliation: Department of Biology, University of California, Riverside, California 91521, USA.
authors.forename: Dmitri A
authors.initials: DA
authors.lastname: Maslov
authors.affiliation: California NanoSystems Institute, University of California, Los Angeles, California 90095, USA.|Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California 90095, USA.
authors.forename: Z Hong
authors.initials: ZH
authors.lastname: Zhou
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D020285:Cryoelectron Microscopy / Q000379:methods*; D006801:Humans; D007893:Leishmania donovani / Q000378:metabolism*; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D010303:Paromomycin / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects; D012335:RNA, Ribosomal / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: D000900:Anti-Bacterial Agents; D012335:RNA, Ribosomal; D010303:Paromomycin