title: Crystal structure of the Varkud satellite ribozyme.
abstract: The Varkud satellite (VS) ribozyme mediates rolling-circle replication of a plasmid found in the Neurospora mitochondrion. We report crystal structures of this ribozyme from Neurospora intermedia at 3.1 Å resolution, which revealed an intertwined dimer formed by an exchange of substrate helices. In each protomer, an arrangement of three-way helical junctions organizes seven helices into a global fold that creates a docking site for the substrate helix of the other protomer, resulting in the formation of two active sites in trans. This mode of RNA-RNA association resembles the process of domain swapping in proteins and has implications for RNA regulation and evolution. Within each active site, adenine and guanine nucleobases abut the scissile phosphate, poised to serve direct roles in catalysis. Similarities to the active sites of the hairpin and hammerhead ribozymes highlight the functional importance of active-site features, underscore the ability of RNA to access functional architectures from distant regions of sequence space, and suggest convergent evolution.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Nikolai B
authors.initials: NB
authors.lastname: Suslov
authors.affiliation: Department of Chemistry, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Saurja
authors.initials: S
authors.lastname: DasGupta
authors.affiliation: Department of Chemistry, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Fuller
authors.affiliation: Cancer Research UK Nucleic Acid Structure Research Group, University of Dundee, Dundee, UK.
authors.forename: David M J
authors.initials: DM
authors.lastname: Lilley
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Phoebe A
authors.initials: PA
authors.lastname: Rice
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois, USA.|Department of Chemistry, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Piccirilli
mesh_terms: D000225:Adenine / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004722:Endoribonucleases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006147:Guanine / Q000737:chemistry / Q000378:metabolism; D008928:Mitochondria / Q000737:chemistry / Q000201:enzymology; D062105:Molecular Docking Simulation; D009154:Mutation; D009491:Neurospora / Q000737:chemistry* / Q000201:enzymology; D009690:Nucleic Acid Conformation; D010710:Phosphates / Q000737:chemistry / Q000378:metabolism; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D012313:RNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016337:RNA, Catalytic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D005656:Fungal Proteins; D010710:Phosphates; D016337:RNA, Catalytic; D011994:Recombinant Proteins; C427204:hammerhead ribozyme; D006147:Guanine; D012313:RNA; D004722:Endoribonucleases; C438195:varkud satellite ribozyme; D000225:Adenine