title: Structure of S5a bound to monoubiquitin provides a model for polyubiquitin recognition.
abstract: Ubiquitin is a key regulatory molecule in diverse cellular events. How cells determine the outcome of ubiquitylation remains unclear; however, a likely determinant is the specificity of ubiquitin receptor proteins for polyubiquitin chains of certain length and linkage. Proteasome subunit S5a contains two ubiquitin-interacting motifs (UIMs) through which it recruits ubiquitylated substrates to the proteasome for their degradation. Here, we report the structure of S5a (196-306) alone and complexed with two monoubiquitin molecules. This construct contains the two UIMs of S5a and we reveal their different ubiquitin-binding mechanisms and provide a rationale for their unique specificities for different ubiquitin-like domains. Furthermore, we provide direct evidence that S5a (196-306) binds either K63-linked or K48-linked polyubiquitin, and in both cases prefers longer chains. On the basis of these results we present a model for how S5a and other ubiquitin-binding proteins recognize polyubiquitin.
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 6-155 Jackson Hall, 321 Church St SE, Minneapolis, MN 55455, USA.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Wang
authors.forename: Patrick
authors.initials: P
authors.lastname: Young
authors.forename: Kylie J
authors.initials: KJ
authors.lastname: Walters
mesh_terms: D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D025821:Polyubiquitin / Q000737:chemistry* / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D016601:RNA-Binding Proteins
chemical_list: D002352:Carrier Proteins; C498506:PSMD4 protein, human; D016601:RNA-Binding Proteins; D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex