title: Defining how ubiquitin receptors hHR23a and S5a bind polyubiquitin.
abstract: Ubiquitin receptors connect substrate ubiquitylation to proteasomal degradation. HHR23a binds proteasome subunit 5a (S5a) through a surface that also binds ubiquitin. We report that UIM2 of S5a binds preferentially to hHR23a over polyubiquitin, and we provide a model for the ternary complex that we expect represents one of the mechanisms used by the proteasome to capture ubiquitylated substrates. Furthermore, we demonstrate that hHR23a is surprisingly adept at sequestering the ubiquitin moieties of a polyubiquitin chain, and provide evidence that it and the ubiquitylated substrate are committed to each other after binding.
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Kang
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Lary
authors.forename: James L
authors.initials: JL
authors.lastname: Cole
authors.forename: Kylie J
authors.initials: KJ
authors.lastname: Walters
mesh_terms: D002850:Chromatography, Gel; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D025821:Polyubiquitin / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C498506:PSMD4 protein, human; D016601:RNA-Binding Proteins; C470301:UBA2 protein, human; D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex; D044764:Ubiquitin-Activating Enzymes