title: Dss1 is a 26S proteasome ubiquitin receptor.
abstract: The ubiquitin-proteasome system is the major pathway for protein degradation in eukaryotic cells. Proteins to be degraded are conjugated to ubiquitin chains that act as recognition signals for the 26S proteasome. The proteasome subunits Rpn10 and Rpn13 are known to bind ubiquitin, but genetic and biochemical data suggest the existence of at least one other substrate receptor. Here, we show that the phylogenetically conserved proteasome subunit Dss1 (Sem1) binds ubiquitin chains linked by K63 and K48. Atomic resolution data show that Dss1 is disordered and binds ubiquitin by binding sites characterized by acidic and hydrophobic residues. The complementary binding region in ubiquitin is composed of a hydrophobic patch formed by I13, I44, and L69 flanked by two basic regions. Mutations in the ubiquitin-binding site of Dss1 cause growth defects and accumulation of ubiquitylated proteins.
authors.affiliation: Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, UK.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Paraskevopoulos
authors.affiliation: Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.
authors.forename: Franziska
authors.initials: F
authors.lastname: Kriegenburg
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Tatham
authors.affiliation: Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.
authors.forename: Heike I
authors.initials: HI
authors.lastname: Rösner
authors.affiliation: Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, UK.
authors.forename: Bethan
authors.initials: B
authors.lastname: Medina
authors.affiliation: Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.
authors.forename: Ida B
authors.initials: IB
authors.lastname: Larsen
authors.affiliation: Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Brandstrup
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, EH9 3JR, Scotland, UK.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Hardwick
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK.
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Hay
authors.affiliation: Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark.
authors.forename: Birthe B
authors.initials: BB
authors.lastname: Kragelund
authors.affiliation: Department of Biology, University of Copenhagen, Ole Maaløes Vej 5, 2200 Copenhagen N, Denmark. Electronic address: rhpetersen@bio.ku.dk.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Hartmann-Petersen
authors.affiliation: Medical Research Council Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, Scotland, UK. Electronic address: colinbgordon@virginmedia.com.
authors.forename: Colin
authors.initials: C
authors.lastname: Gordon
mesh_terms: D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D016601:RNA-Binding Proteins; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000378:metabolism*; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; C508690:Dss1 protein, S pombe; D016601:RNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; D025801:Ubiquitin; C498507:pus1 protein, S pombe; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease