title: Ribosome. The structure of the human mitochondrial ribosome.
abstract: The highly divergent ribosomes of human mitochondria (mitoribosomes) synthesize 13 essential proteins of oxidative phosphorylation complexes. We have determined the structure of the intact mitoribosome to 3.5 angstrom resolution by means of single-particle electron cryogenic microscopy. It reveals 80 extensively interconnected proteins, 36 of which are specific to mitochondria, and three ribosomal RNA molecules. The head domain of the small subunit, particularly the messenger (mRNA) channel, is highly remodeled. Many intersubunit bridges are specific to the mitoribosome, which adopts conformations involving ratcheting or rolling of the small subunit that are distinct from those seen in bacteria or eukaryotes. An intrinsic guanosine triphosphatase mediates a contact between the head and central protuberance. The structure provides a reference for analysis of mutations that cause severe pathologies and for future drug design.
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, United Kingdom.
authors.forename: Alexey
authors.initials: A
authors.lastname: Amunts
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, United Kingdom.
authors.forename: Alan
authors.initials: A
authors.lastname: Brown
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, United Kingdom.
authors.forename: Jaan
authors.initials: J
authors.lastname: Toots
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, United Kingdom.
authors.forename: Sjors H W
authors.initials: SHW
authors.lastname: Scheres
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, United Kingdom.
authors.forename: V
authors.initials: V
authors.lastname: Ramakrishnan
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018360:Crystallography, X-Ray; D024881:Drug Resistance, Bacterial / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000737:chemistry; D030342:Genetic Diseases, Inborn / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D008928:Mitochondria / Q000737:chemistry / Q000648:ultrastructure*; D012333:RNA, Messenger / Q000737:chemistry; D012335:RNA, Ribosomal / Q000737:chemistry; D012269:Ribosomal Proteins / Q000737:chemistry; D012270:Ribosomes / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure*
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D012333:RNA, Messenger; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; D020558:GTP Phosphohydrolases
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