title: The axial channel of the 20S proteasome opens upon binding of the PA200 activator.
abstract: Proteasomes consist of a proteolytic core called the 20 S particle and ancillary factors that regulate its activity in various ways. PA200 has been identified as a large (200 kDa) nuclear protein that stimulates proteasomal hydrolysis of peptides. To characterize its interaction with the 20 S core, we have visualized PA200-20 S complexes by electron microscopy. Monomers of PA200 bind to one or both ends of the 20 S core. Reconstructed in three dimensions to 23 A resolution from cryo-electron micrographs of the singly bound complex, PA200 has an asymmetric dome-like structure with major and minor lobes. Taking into account previous bioinformatic analysis, it is likely to represent an irregular folding of an alpha-helical solenoid composed of HEAT-like repeats. PA200 makes contact with all alpha-subunits except alpha7, and this interaction induces an opening of the axial channel through the alpha-ring. Thus, the activation mechanism of PA200 is expressed via its allosteric effects on the 20 S core particle, perhaps facilitating release of digestion products or the entrance of substrates.
authors.affiliation: Laboratory of Structural Biology, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bldg 50, Room 1517, 50 South Drive MSC 8025, Bethesda, MD 20892-8025, USA.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Ortega
authors.forename: J Bernard
authors.initials: JB
authors.lastname: Heymann
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kajava
authors.forename: Vicença
authors.initials: V
authors.lastname: Ustrell
authors.forename: Martin
authors.initials: M
authors.lastname: Rechsteiner
authors.forename: Alasdair C
authors.initials: AC
authors.lastname: Steven
mesh_terms: D000495:Allosteric Site; D020134:Catalytic Domain; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D020449:Repetitive Sequences, Amino Acid / Q000502:physiology*
chemical_list: D007473:Ion Channels; D046988:Proteasome Endopeptidase Complex