title: Structures of the Dsk2 UBL and UBA domains and their complex.
abstract: The yeast proteins Dsk2 and Rad23 belong to a family of proteins that contain an N-terminal ubiquitin-like domain (UBL) and a C-terminal ubiquitin-associated domain (UBA). Both Dsk2 and Rad23 function as adaptors to target ubiquitin-labelled proteins to the proteasome through recognition of polyubiquitin (four or more K48-linked ubiquitins) by their UBA domains and to the yeast proteasomal subunit Rpn1 by their UBL domains. The crystal structures of the Dsk2 UBL domain, the Dsk2 UBA domain and the Dsk2 UBA-UBL complex are reported. In the crystal, the Dsk2 UBA domains associate through electrostatic interactions to form ninefold helical ribbons that leave the ubiquitin-binding surface exposed. The UBA-UBL complex explains the reduced affinity of the UBA domain for UBL compared with ubiquitin and has implications for the regulation of Dsk2 adaptor function during ubiquitin-mediated proteasomal targeting. A model is discussed in which two or more Dsk2 UBA molecules may selectively bind to K48-linked polyubiquitin.
authors.affiliation: Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, England.
authors.forename: Edward D
authors.initials: ED
authors.lastname: Lowe
authors.forename: Na'il
authors.initials: N
authors.lastname: Hasan
authors.forename: Jean Francois
authors.initials: JF
authors.lastname: Trempe
authors.forename: Laura
authors.initials: L
authors.lastname: Fonso
authors.forename: Martin E M
authors.initials: ME
authors.lastname: Noble
authors.forename: Jane A
authors.initials: JA
authors.lastname: Endicott
authors.forename: Louise N
authors.initials: LN
authors.lastname: Johnson
authors.forename: Nick R
authors.initials: NR
authors.lastname: Brown
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003460:Crystallization; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D025821:Polyubiquitin / Q000737:chemistry / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance; D014452:Ubiquitins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C100415:DSK2 protein, S cerevisiae; C490846:RAD23 protein, S cerevisiae; C499663:RPN1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex