Structure of a Cytoplasmic 11-Subunit RNA Exosome Complex

Eva Kowalinski; Alexander Kögel; Judith Ebert; Peter Reichelt; Elisabeth Stegmann; Bianca Habermann; Elena Conti

doi:10.1016/j.molcel.2016.05.028

Structure of a Cytoplasmic 11-Subunit RNA Exosome Complex

Mol Cell. 2016 Jul 7;63(1):125-34. doi: 10.1016/j.molcel.2016.05.028. Epub 2016 Jun 23.

Authors

Eva Kowalinski¹, Alexander Kögel¹, Judith Ebert¹, Peter Reichelt¹, Elisabeth Stegmann¹, Bianca Habermann², Elena Conti³

Affiliations

¹ Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
² Computational Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
³ Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany. Electronic address: [email protected].

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.

MeSH terms

Adaptor Proteins, Signal Transducing / chemistry
Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism*
Amino Acid Sequence
Binding Sites
Conserved Sequence
Evolution, Molecular
Exosome Multienzyme Ribonuclease Complex / chemistry
Exosome Multienzyme Ribonuclease Complex / genetics
Exosome Multienzyme Ribonuclease Complex / metabolism*
GTP-Binding Proteins / genetics
GTP-Binding Proteins / metabolism*
HSP70 Heat-Shock Proteins / genetics
HSP70 Heat-Shock Proteins / metabolism*
Humans
Hydrophobic and Hydrophilic Interactions
Models, Molecular
Mutation
Nuclear Proteins / metabolism
Peptide Elongation Factors / genetics
Peptide Elongation Factors / metabolism*
Protein Binding
Protein Conformation
Protein Interaction Domains and Motifs
Protein Isoforms
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / chemistry
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism*
Structure-Activity Relationship

Substances

Adaptor Proteins, Signal Transducing
CSL4 protein, S cerevisiae
HSP70 Heat-Shock Proteins
Nuclear Proteins
Peptide Elongation Factors
Protein Isoforms
SKI7 protein, S cerevisiae
Saccharomyces cerevisiae Proteins
Exosome Multienzyme Ribonuclease Complex
MTR3 protein, S cerevisiae
RRP6 protein, S cerevisiae
GTP-Binding Proteins
HBS1L protein, human