title: Investigations on the maturation and regulation of archaebacterial proteasomes.
abstract: The 20S proteasome (core particle, CP) is a multifunctional protease complex and composed of four heptameric subunit rings arranged in a hollow, barrel-shaped structure. Here, we report the crystal structure of the CP from Archaeoglobus fulgidus at 2.25A resolution. The analysis of the structure of early and late assembly intermediates of this CP gives new insights in the maturation of archaebacterial CPs and indicates similarities to assembly intermediates observed in eukaryotes. We also show a striking difference in mechanism and regulation of substrate access between eukaryotic and archaebacterial 20S proteasomes. While eukaryotic CPs are auto-inhibited by the N-terminal tails of the outer alpha-ring by imposing topological closure with a characteristic sequence motif (YDR-motif) and show regulatory gating this segment is disordered in the CP and differently structured in the alpha(7)-sub-complex of A.fulgidus leaving a pore leading into the particle with a diameter of 13A. Mutagenesis and functional studies indicate the absence of regulatory gating in the archaeal 20S proteasome.
authors.affiliation: Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, D-82152 Planegg-Martinsried, Germany. groll@biochem.mpg.de
authors.forename: Michael
authors.initials: M
authors.lastname: Groll
authors.forename: Hans
authors.initials: H
authors.lastname: Brandstetter
authors.forename: Hans
authors.initials: H
authors.lastname: Bartunik
authors.forename: Gleb
authors.initials: G
authors.lastname: Bourenkow
authors.forename: Robert
authors.initials: R
authors.lastname: Huber
mesh_terms: D000595:Amino Acid Sequence; D019843:Archaeal Proteins / Q000737:chemistry* / Q000378:metabolism*; D019611:Archaeoglobus fulgidus / Q000378:metabolism*; D003001:Cloning, Molecular; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D020836:Protein Structure, Quaternary; D021122:Protein Subunits; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
chemical_list: D019843:Archaeal Proteins; D009097:Multienzyme Complexes; D021122:Protein Subunits; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex