title: The structure of the 26S proteasome subunit Rpn2 reveals its PC repeat domain as a closed toroid of two concentric α-helical rings.
abstract: The 26S proteasome proteolyses ubiquitylated proteins and is assembled from a 20S proteolytic core and two 19S regulatory particles (19S-RP). The 19S-RP scaffolding subunits Rpn1 and Rpn2 function to engage ubiquitin receptors. Rpn1 and Rpn2 are characterized by eleven tandem copies of a 35-40 amino acid repeat motif termed the proteasome/cyclosome (PC) repeat. Here, we reveal that the eleven PC repeats of Rpn2 form a closed toroidal structure incorporating two concentric rings of α helices encircling two axial α helices. A rod-like N-terminal domain consisting of 17 stacked α helices and a globular C-terminal domain emerge from one face of the toroid. Rpn13, an ubiquitin receptor, binds to the C-terminal 20 residues of Rpn2. Rpn1 adopts a similar conformation to Rpn2 but differs in the orientation of its rod-like N-terminal domain. These findings have implications for understanding how 19S-RPs recognize, unfold, and deliver ubiquitylated substrates to the 20S core.
authors.affiliation: Division of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, United Kingdom.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.forename: Kiran
authors.initials: K
authors.lastname: Kulkarni
authors.forename: Paula C A
authors.initials: PC
authors.lastname: da Fonseca
authors.forename: Dasha
authors.initials: D
authors.lastname: Krutauz
authors.forename: Michael H
authors.initials: MH
authors.lastname: Glickman
authors.forename: David
authors.initials: D
authors.lastname: Barford
authors.forename: Edward P
authors.initials: EP
authors.lastname: Morris
mesh_terms: D000595:Amino Acid Sequence; D006602:Hexosyltransferases; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D016415:Sequence Alignment; D020080:Tandem Repeat Sequences / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D025801:Ubiquitin; D006602:Hexosyltransferases; C517590:RPN2 protein, human; D046988:Proteasome Endopeptidase Complex