title: The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together.
abstract: Proteasomes execute the degradation of most cellular proteins. Although the 20S core particle (CP) has been studied in great detail, the structure of the 19S regulatory particle (RP), which prepares ubiquitylated substrates for degradation, has remained elusive. Here, we report the crystal structure of one of the RP subunits, Rpn6, and we describe its integration into the cryo-EM density map of the 26S holocomplex at 9.1 Å resolution. Rpn6 consists of an α-solenoid-like fold and a proteasome COP9/signalosome eIF3 (PCI) module in a right-handed suprahelical configuration. Highly conserved surface areas of Rpn6 interact with the conserved surfaces of the Pre8 (alpha2) and Rpt6 subunits from the alpha and ATPase rings, respectively. The structure suggests that Rpn6 has a pivotal role in stabilizing the otherwise weak interaction between the CP and the RP.
authors.affiliation: Department of Molecular Structural Biology, Max-Planck-Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany.
authors.forename: Ganesh Ramnath
authors.initials: GR
authors.lastname: Pathare
authors.forename: István
authors.initials: I
authors.lastname: Nagy
authors.forename: Stefan
authors.initials: S
authors.lastname: Bohn
authors.forename: Pia
authors.initials: P
authors.lastname: Unverdorben
authors.forename: Agnes
authors.initials: A
authors.lastname: Hubert
authors.forename: Roman
authors.initials: R
authors.lastname: Körner
authors.forename: Stephan
authors.initials: S
authors.lastname: Nickell
authors.forename: Keren
authors.initials: K
authors.lastname: Lasker
authors.forename: Andrej
authors.initials: A
authors.lastname: Sali
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tamura
authors.forename: Taiki
authors.initials: T
authors.lastname: Nishioka
authors.forename: Friedrich
authors.initials: F
authors.lastname: Förster
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumeister
authors.forename: Andreas
authors.initials: A
authors.lastname: Bracher
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000201:enzymology; D012996:Solutions; D013499:Surface Properties
chemical_list: D029721:Drosophila Proteins; D046912:Multiprotein Complexes; D021122:Protein Subunits; C470518:Rpn6 protein, Drosophila; D012996:Solutions; D046988:Proteasome Endopeptidase Complex