Hexameric assembly of the proteasomal ATPases is templated through their C termini

被引:112
作者
Park, Soyeon [1 ]
Roelofs, Jeroen [1 ]
Kim, Woong [1 ]
Robert, Jessica [1 ]
Schmidt, Marion [2 ]
Gygi, Steven P. [1 ]
Finley, Daniel [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
[2] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA
基金
美国国家卫生研究院;
关键词
19S REGULATORY PARTICLE; 26; S-PROTEASOME; 20S PROTEASOMES; STRUCTURAL BASIS; COMPLEX; YEAST; PROTEINS; SUBUNITS; PATHWAY; DEGRADATION;
D O I
10.1038/nature08065
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Substrates of the proteasome are recognized and unfolded by the regulatory particle, and then translocated into the core particle (CP) to be degraded(1). A hetero-hexameric ATPase ring, containing subunits Rpt1-6, is situated within the base subassembly of the regulatory particle(1). The ATPase ring sits atop the CP, with the Rpt carboxy termini inserted into pockets in the CP2-6. Here we identify a previously unknown function of the Rpt proteins in proteasome biogenesis through deleting the C-terminal residue from each Rpt in the yeast Saccharomyces cerevisiae. Our results indicate that assembly of the hexameric ATPase ring is templated on the CP. We have also identified an apparent intermediate in base assembly, BP1, which contains Rpn1, three Rpts and Hsm3, a chaperone for base assembly. The Rpt proteins with the strongest assembly phenotypes, Rpt4 and Rpt6, were absent from BP1. We propose that Rpt4 and Rpt6 form a nucleating complex to initiate base assembly, and that this complex is subsequently joined by BP1 to complete the Rpt ring. Our studies show that assembly of the proteasome base is a rapid yet highly orchestrated process.
引用
收藏
页码:866 / U9
页数:6
相关论文
共 30 条
[1]   20S proteasome and its inhibitors: Crystallographic knowledge for drug development [J].
Borissenko, Ljudmila ;
Groll, Michael .
CHEMICAL REVIEWS, 2007, 107 (03) :687-717
[2]   Gankyrin is an ankyrin-repeat oncoprotein that interacts with CDK4 kinase and the S6 ATPase of the 26 S proteasome [J].
Dawson, S ;
Apcher, S ;
Mee, M ;
Higashitsuji, H ;
Baker, R ;
Uhle, S ;
Dubiel, W ;
Fujita, J ;
Mayer, RJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (13) :10893-10902
[3]   AN APPROACH TO CORRELATE TANDEM MASS-SPECTRAL DATA OF PEPTIDES WITH AMINO-ACID-SEQUENCES IN A PROTEIN DATABASE [J].
ENG, JK ;
MCCORMACK, AL ;
YATES, JR .
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY, 1994, 5 (11) :976-989
[4]   Recognition and Processing of Ubiquitin-Protein Conjugates by the Proteasome [J].
Finley, Daniel .
ANNUAL REVIEW OF BIOCHEMISTRY, 2009, 78 :477-513
[5]   The 1.9 A structure of a proteasome-11S activator complex and implications for proteasome-PAN/PA700 interactions [J].
Förster, A ;
Masters, EI ;
Whitby, FG ;
Robinson, H ;
Hill, CP .
MOLECULAR CELL, 2005, 18 (05) :589-599
[6]   Differential Roles of the COOH Termini of AAA Subunits of PA700 (19 S Regulator) in Asymmetric Assembly and Activation of the 26 S Proteasome [J].
Gillette, Thomas G. ;
Kumar, Brajesh ;
Thompson, David ;
Slaughter, Clive A. ;
DeMartino, George N. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (46) :31813-31822
[7]   A subcomplex of the proteasome regulatory particle required for ubiquitin-conjugate degradation and related to the COP9-signalosome and eIF3 [J].
Glickman, MH ;
Rubin, DM ;
Coux, O ;
Wefes, I ;
Pfeifer, G ;
Cjeka, Z ;
Baumeister, W ;
Fried, VA ;
Finley, D .
CELL, 1998, 94 (05) :615-623
[8]   Mapping subunit contacts in the regulatory complex of the 26 S proteasome - S2 and S5b form a tetramer with ATPase subunits S4 and S7 [J].
Gorbea, C ;
Taillandier, D ;
Rechsteiner, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (02) :875-882
[9]  
Guthrie C., 1991, GUIDE YEAST GENETICS
[10]   Deubiquitinating enzyme Ubp6 functions noncatalytically to delay proteasomal degradation [J].
Hanna, John ;
Hathaway, Nathaniel A. ;
Tone, Yoshiko ;
Crosas, Bernat ;
Elsasser, Suzanne ;
Kirkpatrick, Donald S. ;
Leggett, David S. ;
Gygi, Steven P. ;
King, Randall W. ;
Finley, Daniel .
CELL, 2006, 127 (01) :99-111