title: Defining the geometry of the two-component proteasome degron.
abstract: The eukaryotic 26S proteasome controls cellular processes by degrading specific regulatory proteins. Most proteins are targeted for degradation by a signal or degron that consists of two parts: a proteasome-binding tag, typically covalently attached polyubiquitin chains, and an unstructured region that serves as the initiation region for proteasomal proteolysis. Here we have characterized how the arrangement of the two degron parts in a protein affects degradation. We found that a substrate is degraded efficiently only when its initiation region is of a certain minimal length and is appropriately separated in space from the proteasome-binding tag. Regions that are located too close or too far from the proteasome-binding tag cannot access the proteasome and induce degradation. These spacing requirements are different for a polyubiquitin chain and a ubiquitin-like domain. Thus, the arrangement and location of the proteasome initiation region affect a protein's fate and are important in selecting proteins for proteasome-mediated degradation.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, USA.
authors.forename: Tomonao
authors.initials: T
authors.lastname: Inobe
authors.forename: Susan
authors.initials: S
authors.lastname: Fishbain
authors.forename: Sumit
authors.initials: S
authors.lastname: Prakash
authors.forename: Andreas
authors.initials: A
authors.lastname: Matouschek
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000378:metabolism; D009492:Neurospora crassa / Q000378:metabolism; D025821:Polyubiquitin / Q000737:chemistry / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D029968:Escherichia coli Proteins; D007136:Immunoglobulins; D025821:Polyubiquitin; D046988:Proteasome Endopeptidase Complex