title: Structure of a Cytoplasmic 11-Subunit RNA Exosome Complex.
abstract: The RNA exosome complex associates with nuclear and cytoplasmic cofactors to mediate the decay, surveillance, or processing of a wide variety of transcripts. In the cytoplasm, the conserved core of the exosome (Exo10) functions together with the conserved Ski complex. The interaction of S. cerevisiae Exo10 and Ski is not direct but requires a bridging cofactor, Ski7. Here, we report the 2.65 Å resolution structure of S. cerevisiae Exo10 bound to the interacting domain of Ski7. Extensive hydrophobic interactions rationalize the high affinity and stability of this complex, pointing to Ski7 as a constitutive component of the cytosolic exosome. Despite the absence of sequence homology, cytoplasmic Ski7 and nuclear Rrp6 bind Exo10 using similar surfaces and recognition motifs. Knowledge of the interacting residues in the yeast complexes allowed us to identify a splice variant of human HBS1-Like as a Ski7-like exosome-binding protein, revealing the evolutionary conservation of this cytoplasmic cofactor.
authors.affiliation: Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Kowalinski
authors.affiliation: Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kögel
authors.affiliation: Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Ebert
authors.affiliation: Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Reichelt
authors.affiliation: Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Stegmann
authors.affiliation: Computational Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Habermann
authors.affiliation: Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany. Electronic address: conti@biochem.mpg.de.
authors.forename: Elena
authors.initials: E
authors.lastname: Conti
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D019143:Evolution, Molecular; D063326:Exosome Multienzyme Ribonuclease Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D010445:Peptide Elongation Factors / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C112809:CSL4 protein, S cerevisiae; D018840:HSP70 Heat-Shock Proteins; D009687:Nuclear Proteins; D010445:Peptide Elongation Factors; D020033:Protein Isoforms; C118668:SKI7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D063326:Exosome Multienzyme Ribonuclease Complex; C097433:MTR3 protein, S cerevisiae; C112610:RRP6 protein, S cerevisiae; D019204:GTP-Binding Proteins; C000628258:HBS1L protein, human