title: Usa1 functions as a scaffold of the HRD-ubiquitin ligase.
abstract: Protein quality control in the endoplasmic reticulum is of central importance for cellular homeostasis in eukaryotes. Crucial for this process is the HRD-ubiquitin ligase (HMG-CoA reductase degradation), which singles out terminally misfolded proteins and routes them for degradation to cytoplasmic 26S-proteasomes. Certain functions of this enzyme complex are allocated to defined subunits. However, it remains unclear how these components act in a concerted manner. Here, we show that Usa1 functions as a major scaffold protein of the HRD-ligase. For the turnover of soluble substrates, Der1 binding to the C terminus of Usa1 is required. The N terminus of Usa1 associates with Hrd1 and thus bridges Der1 to Hrd1. Strikingly, the Usa1 N terminus also induces oligomerization of the HRD complex, which is an exclusive prerequisite for the degradation of membrane proteins. Our data demonstrate that scaffold proteins are required to adapt ubiquitin ligase activities toward different classes of substrates.
authors.affiliation: Max-Delbrück Center for Molecular Medicine, 13125 Berlin, Germany.
authors.forename: Sabine C
authors.initials: SC
authors.lastname: Horn
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hanna
authors.forename: Christian
authors.initials: C
authors.lastname: Hirsch
authors.forename: Corinna
authors.initials: C
authors.lastname: Volkwein
authors.forename: Anja
authors.initials: A
authors.lastname: Schütz
authors.forename: Udo
authors.initials: U
authors.lastname: Heinemann
authors.forename: Thomas
authors.initials: T
authors.lastname: Sommer
authors.forename: Ernst
authors.initials: E
authors.lastname: Jarosch
mesh_terms: D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D025941:Protein Interaction Mapping; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D015003:Yeasts / Q000378:metabolism*
chemical_list: D005656:Fungal Proteins; D044767:Ubiquitin-Protein Ligases