TY - JOUR
T1 - The HEAT repeat protein Blm10 regulates the yeast proteasome by capping the core particle
AU - Schmidt, Marion
AU - Haas, Wilhelm
AU - Crosas, Bernat
AU - Santamaria, Patricia G.
AU - Gygi, Steven P.
AU - Walz, Thomas
AU - Finley, Daniel
N1 - Funding Information:
This work was supported by a grant from the Deutsche Forschungsgemeinschaft to M.S. (SCHM 884/3-1), and US National Institutes of Health (NIH) grants to D.F. (GM65592) and S.G. (GM67945). We thank B. Petre for collecting the EM images. The molecular EM facility at Harvard Medical School was established by a generous donation from the Giovanni Armenise Harvard Center for Structural Biology and is maintained by funds from NIH grant GM62580 to T.W. We are also grateful to the Harvard Medical School Nikon Imaging Center for technical assistance and access to their instruments, to R. Li for providing us with an antibody against Arc15, and to S. Elsasser, J. Hanna and J. Roelofs for critical reading of the manuscript. We thank R. Gali, and the Bauer Center for Genomics Research, Harvard University, for help with preliminary results of microarray analysis on the Rosetta Resolver microarray analysis platform. We furthermore are grateful to C. Hill for communicating results prior to publication and to A.L. Goldberg for his permission to include PA28-20S electron micrographs in our study.
PY - 2005
Y1 - 2005
N2 - Proteasome activity is fine-tuned by associating the proteolytic core particle (CP) with stimulatory and inhibitory complexes. Although several mammalian regulatory complexes are known, knowledge of yeast proteasome regulators is limited to the 19-subunit regulatory particle (RP), which confers ubiquitin-dependence on proteasomes. Here we describe an alternative proteasome activator from Saccharomyces cerevisiae, Blm10. Synthetic interactions between blm10Δ and other mutations that impair proteasome function show that Blm10 functions together with proteasomes in vivo. This large, internally repetitive protein is found predominantly within hybrid Blm10-CP-RP complexes, representing a distinct pool of mature proteasomes. EM studies show that Blm10 has a highly elongated, curved structure. The near-circular profile of Blm10 adapts it to the end of the CP cylinder, where it is properly positioned to activate the CP by opening the axial channel into its proteolytic chamber.
AB - Proteasome activity is fine-tuned by associating the proteolytic core particle (CP) with stimulatory and inhibitory complexes. Although several mammalian regulatory complexes are known, knowledge of yeast proteasome regulators is limited to the 19-subunit regulatory particle (RP), which confers ubiquitin-dependence on proteasomes. Here we describe an alternative proteasome activator from Saccharomyces cerevisiae, Blm10. Synthetic interactions between blm10Δ and other mutations that impair proteasome function show that Blm10 functions together with proteasomes in vivo. This large, internally repetitive protein is found predominantly within hybrid Blm10-CP-RP complexes, representing a distinct pool of mature proteasomes. EM studies show that Blm10 has a highly elongated, curved structure. The near-circular profile of Blm10 adapts it to the end of the CP cylinder, where it is properly positioned to activate the CP by opening the axial channel into its proteolytic chamber.
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U2 - 10.1038/nsmb914
DO - 10.1038/nsmb914
M3 - Article
C2 - 15778719
AN - SCOPUS:18744391955
SN - 1545-9993
VL - 12
SP - 294
EP - 303
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
IS - 4
ER -