Proteasome activators

Molecular Cell

Volumn 41, Issue 1, 2011, Pages 8-19

  Stadtmueller, Beth M ^a   Hill, Christopher P ^a  

^a UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

11S PROTEASOME; 19 S PROTEASOME; 26S PROTEASOME; POLYUBIQUITIN; PROTEASOME; PROTEIN BLM10; SACCHAROMYCES CEREVISIAE PROTEIN; UNCLASSIFIED DRUG;

CRYSTAL STRUCTURE; DICTYOSTELIUM DISCOIDEUM; EUKARYOTE; HYDROLYSIS; NONHUMAN; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN FOLDING; PROTEIN STRUCTURE; REVIEW; TRYPANOSOMA BRUCEI;

BACTERIAL PROTEINS; ENZYME ACTIVATORS; MODELS, MOLECULAR; POLYUBIQUITIN; PROTEASOME ENDOPEPTIDASE COMPLEX; PROTEIN SUBUNITS; PROTEIN UNFOLDING; SACCHAROMYCES CEREVISIAE PROTEINS; UBIQUITINATION;

EID: 78650720758     PISSN: 10972765     EISSN: 10974164     Source Type: Journal    
DOI: 10.1016/j.molcel.2010.12.020     Document Type: Review

References (101)

1. Babbitt S.E., Kiss A., Deffenbaugh A.E., Chang Y.H., Bailly E., Erdjument-Bromage H., Tempst P., Buranda T., Sklar L.A., Baumler J., et al. ATP hydrolysis-dependent disassembly of the 26S proteasome is part of the catalytic cycle. Cell 2005, 121:553-565.
2. Bajorek M., Finley D., Glickman M.H. Proteasome disassembly and downregulation is correlated with viability during stationary phase. Curr. Biol. 2003, 13:1140-1144.
3. Baugh J.M., Viktorova E.G., Pilipenko E.V. Proteasomes can degrade a significant proportion of cellular proteins independent of ubiquitination. J. Mol. Biol. 2009, 386:814-827.
4. Bech-Otschir D., Helfrich A., Enenkel C., Consiglieri G., Seeger M., Holzhutter H.G., Dahlmann B., Kloetzel P.M. Polyubiquitin substrates allosterically activate their own degradation by the 26S proteasome. Nat. Struct. Mol. Biol. 2009, 16:219-225.
5. Benaroudj N., Zwickl P., Seemuller E., Baumeister W., Goldberg A.L. ATP hydrolysis by the proteasome regulatory complex PAN serves multiple functions in protein degradation. Mol. Cell 2003, 11:69-78.
6. Blickwedehl J., Agarwal M., Seong C., Pandita R.K., Melendy T., Sung P., Pandita T.K., Bangia N. Role for proteasome activator PA200 and postglutamyl proteasome activity in genomic stability. Proc. Natl. Acad. Sci. USA 2008, 105:16165-16170.
7. Bochtler M., Hartmann C., Song H.K., Bourenkov G.P., Bartunik H.D., Huber R. The structures of HsIU and the ATP-dependent protease HsIU-HsIV. Nature 2000, 403:800-805.
8. Bohn S., Beck F., Sakata E., Walzthoeni T., Beck M., Aebersold R., Forster F., Baumeister W., Nickell S. From the cover: structure of the 26S proteasome from Schizosaccharomyces pombe at subnanometer resolution. Proc. Natl. Acad. Sci. USA 2010, 107:20992-20997.
9. Brannigan J.A., Dodson G., Duggleby H.J., Moody P.C., Smith J.L., Tomchick D.R., Murzin A.G. A protein catalytic framework with an N-terminal nucleophile is capable of self-activation. Nature 1995, 378:416-419.
10. Burns K.E., Pearce M.J., Darwin K.H. Prokaryotic ubiquitin-like protein provides a two-part degron to Mycobacterium proteasome substrates. J. Bacteriol. 2010, 192:2933-2935.
11. Chen X., Lee B.H., Finley D., Walters K.J. Structure of proteasome ubiquitin receptor hRpn13 and its activation by the scaffolding protein hRpn2. Mol. Cell 2010, 38:404-415.
12. Cooper E.M., Cutcliffe C., Kristiansen T.Z., Pandey A., Pickart C.M., Cohen R.E. K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated Brcc36 and proteasomal Poh1. EMBO J. 2009, 28:621-631.
13. da Fonseca P.C., Morris E.P. Structure of the human 26S proteasome: subunit radial displacements open the gate into the proteolytic core. J. Biol. Chem. 2008, 283:23305-23314.
14. DeLano W.L. The PyMOL Molecular Graphics System 2002, DeLano Scientific, San Carlos, CA:.
15. Djuranovic S., Hartmann M.D., Habeck M., Ursinus A., Zwickl P., Martin J., Lupas A.N., Zeth K. Structure and activity of the N-terminal substrate recognition domains in proteasomal ATPases. Mol. Cell 2009, 34:580-590.
16. Enemark E.J., Joshua-Tor L. Mechanism of DNA translocation in a replicative hexameric helicase. Nature 2006, 442:270-275.
17. Erzberger J.P., Berger J.M. Evolutionary relationships and structural mechanisms of AAA+ proteins. Annu. Rev. Biophys. Biomol. Struct. 2006, 35:93-114.
18. Fehlker M., Wendler P., Lehmann A., Enenkel C. Blm3 is part of nascent proteasomes and is involved in a late stage of nuclear proteasome assembly. EMBO Rep. 2003, 4:959-963.
19. Finley D. Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu. Rev. Biochem. 2009, 78:477-513.
20. Forster A., Whitby F.G., Hill C.P. The pore of activated 20S proteasomes has an ordered 7-fold symmetric conformation. EMBO J. 2003, 22:4356-4364.
21. Forster A., Masters E.I., Whitby F.G., Robinson H., Hill C.P. The 1.9 Å structure of a proteasome-11S activator complex and implications for proteasome-PAN/PA700 interactions. Mol. Cell 2005, 18:589-599.
22. Forster F., Lasker K., Nickell S., Sali A., Baumeister W. Towards an integrated structural model of the 26S proteasome. Mol. Cell. Proteomics 2010, 9:1666-1677.
23. Gai D., Zhao R., Li D., Finkielstein C.V., Chen X.S. Mechanisms of conformational change for a replicative hexameric helicase of SV40 large tumor antigen. Cell 2004, 119:47-60.
24. Gillette T.G., Kumar B., Thompson D., Slaughter C.A., DeMartino G.N. 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. Biol. Chem. 2008, 283:31813-31822.
25. Glickman M.H., Rubin D.M., Coux O., Wefes I., Pfeifer G., Cjeka Z., Baumeister W., Fried V.A., Finley D. A subcomplex of the proteasome regulatory particle required for ubiquitin-conjugate degradation and related to the COP9-signalosome and eIF3. Cell 1998, 94:615-623.
26. Groettrup M., Kirk C.J., Basler M. Proteasomes in immune cells: more than peptide producers?. Nat. Rev. Immunol. 2010, 10:73-78.
27. Groll M., Ditzel L., Lowe J., Stock D., Bochtler M., Bartunik H.D., Huber R. Structure of 20S proteasome from yeast at 2.4 Å resolution. Nature 1997, 386:463-471.
28. Groll M., Bajorek M., Kohler A., Moroder L., Rubin D.M., Huber R., Glickman M.H., Finley D. A gated channel into the proteasome core particle. Nat. Struct. Biol. 2000, 7:1062-1067.
29. Groll M., Berkers C.R., Ploegh H.L., Ovaa H. Crystal structure of the boronic acid-based proteasome inhibitor bortezomib in complex with the yeast 20S proteasome. Structure 2006, 14:451-456.
30. Groll M., Huber R., Moroder L. The persisting challenge of selective and specific proteasome inhibition. J. Pept. Sci. 2009, 15:58-66.
31. Humbard M.A., Miranda H.V., Lim J.M., Krause D.J., Pritz J.R., Zhou G., Chen S., Wells L., Maupin-Furlow J.A. Ubiquitin-like small archaeal modifier proteins (SAMPs) in Haloferax volcanii. Nature 2010, 463:54-60.
32. Isasa M., Katz E.J., Kim W., Yugo V., Gonzalez S., Kirkpatrick D.S., Thomson T.M., Finley D., Gygi S.P., Crosas B. Monoubiquitination of RPN10 regulates substrate recruitment to the proteasome. Mol. Cell 2010, 38:733-745.
33. Iwanczyk J., Sadre-Bazzaz K., Ferrell K., Kondrashkina E., Formosa T., Hill C.P., Ortega J. Structure of the Blm10-20 S proteasome complex by cryo-electron microscopy. Insights into the mechanism of activation of mature yeast proteasomes. J. Mol. Biol. 2006, 363:648-659.
34. Khor B., Bredemeyer A.L., Huang C.Y., Turnbull I.R., Evans R., Maggi L.B., White J.M., Walker L.M., Carnes K., Hess R.A., Sleckman B.P. Proteasome activator PA200 is required for normal spermatogenesis. Mol. Cell. Biol. 2006, 26:2999-3007.
35. Kisselev A.F., Garcia-Calvo M., Overkleeft H.S., Peterson E., Pennington M.W., Ploegh H.L., Thornberry N.A., Goldberg A.L. The caspase-like sites of proteasomes, their substrate specificity, new inhibitors and substrates, and allosteric interactions with the trypsin-like sites. J. Biol. Chem. 2003, 278:35869-35877.
36. Kleijnen M.F., Roelofs J., Park S., Hathaway N.A., Glickman M., King R.W., Finley D. Stability of the proteasome can be regulated allosterically through engagement of its proteolytic active sites. Nat. Struct. Mol. Biol. 2007, 14:1180-1188.
37. Knowlton J.R., Johnston S.C., Whitby F.G., Realini C., Zhang Z., Rechsteiner M., Hill C.P. Structure of the proteasome activator REGalpha (PA28alpha). Nature 1997, 390:639-643.
38. Kriegenburg F., Seeger M., Saeki Y., Tanaka K., Lauridsen A.M., Hartmann-Petersen R., Hendil K.B. Mammalian 26S proteasomes remain intact during protein degradation. Cell 2008, 135:355-365.
39. Kwon Y.D., Nagy I., Adams P.D., Baumeister W., Jap B.K. Crystal structures of the Rhodococcus proteasome with and without its pro-peptides: implications for the role of the pro-peptide in proteasome assembly. J. Mol. Biol. 2004, 335:233-245.
40. Lam Y.A., DeMartino G.N., Pickart C.M., Cohen R.E. Specificity of the ubiquitin isopeptidase in the PA700 regulatory complex of 26 S proteasomes. J. Biol. Chem. 1997, 272:28438-28446.
41. Lee B.H., Lee M.J., Park S., Oh D.C., Elsasser S., Chen P.C., Gartner C., Dimova N., Hanna J., Gygi S.P., et al. Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature 2010, 467:179-184.
42. Leggett D.S., Hanna J., Borodovsky A., Crosas B., Schmidt M., Baker R.T., Walz T., Ploegh H., Finley D. Multiple associated proteins regulate proteasome structure and function. Mol. Cell 2002, 10:495-507.
43. Lehmann A., Jechow K., Enenkel C. Blm10 binds to pre-activated proteasome core particles with open gate conformation. EMBO Rep. 2008, 9:1237-1243.
44. Li X., Demartino G.N. Variably modulated gating of the 26S proteasome by ATP and polyubiquitin. Biochem. J. 2009, 421:397-404.
45. Li J., Gao X., Ortega J., Nazif T., Joss L., Bogyo M., Steven A.C., Rechsteiner M. Lysine 188 substitutions convert the pattern of proteasome activation by REGgamma to that of REGs alpha and beta. EMBO J. 2001, 20:3359-3369.
46. Li D., Li H., Wang T., Pan H., Lin G. Structural basis for the assembly and gate closure mechanisms of the Mycobacterium tuberculosis 20S proteasome. EMBO J. 2010, 29:2037-2047.
47. Lin G., Li D., de Carvalho L.P., Deng H., Tao H., Vogt G., Wu K., Schneider J., Chidawanyika T., Warren J.D., et al. Inhibitors selective for mycobacterial versus human proteasomes. Nature 2009, 461:621-626.
48. Liu C.W., Li X., Thompson D., Wooding K., Chang T.L., Tang Z., Yu H., Thomas P.J., DeMartino G.N. ATP binding and ATP hydrolysis play distinct roles in the function of 26S proteasome. Mol. Cell 2006, 24:39-50.
49. Lowe J., Stock D., Jap B., Zwickl P., Baumeister W., Huber R. Crystal structure of the 20S proteasome from the archaeon T. acidophilum at 3.4 Å resolution. Science 1995, 268:533-539.
50. Ma C.P., Willy P.J., Slaughter C.A., DeMartino G.N. PA28, an activator of the 20 S proteasome, is inactivated by proteolytic modification at its carboxyl terminus. J. Biol. Chem. 1993, 268:22514-22519.
51. Mao I., Liu J., Li X., Luo H. REGgamma, a proteasome activator and beyond?. Cell. Mol. Life Sci. 2008, 65:3971-3980.
52. Martin A., Baker T.A., Sauer R.T. Rebuilt AAA + motors reveal operating principles for ATP-fuelled machines. Nature 2005, 437:1115-1120.
53. Masson P., Lundin D., Soderbom F., Young P. Characterization of a REG/PA28 proteasome activator homolog in Dictyostelium discoideum indicates that the ubiquitin- and ATP-independent REGgamma proteasome is an ancient nuclear protease. Eukaryot. Cell 2009, 8:844-851.
54. Muchamuel T., Basler M., Aujay M.A., Suzuki E., Kalim K.W., Lauer C., Sylvain C., Ring E.R., Shields J., Jiang J., et al. A selective inhibitor of the immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of experimental arthritis. Nat. Med. 2009, 15:781-787.
55. Murata S., Sasaki K., Kishimoto T., Niwa S., Hayashi H., Takahama Y., Tanaka K. Regulation of CD8+ T cell development by thymus-specific proteasomes. Science 2007, 316:1349-1353.
56. Murata S., Yashiroda H., Tanaka K. Molecular mechanisms of proteasome assembly. Nat. Rev. Mol. Cell Biol. 2009, 10:104-115.
57. Nickell S., Beck F., Scheres S.H., Korinek A., Forster F., Lasker K., Mihalache O., Sun N., Nagy I., Sali A., et al. Insights into the molecular architecture of the 26S proteasome. Proc. Natl. Acad. Sci. USA 2009, 106:11943-11947.
58. Nie J., Wu M., Wang J., Xing G., He F., Zhang L. REGgamma proteasome mediates degradation of the ubiquitin ligase Smurf1. FEBS Lett. 2010, 584:3021-3027.
59. Ortega J., Heymann J.B., Kajava A.V., Ustrell V., Rechsteiner M., Steven A.C. The axial channel of the 20S proteasome opens upon binding of the PA200 activator. J. Mol. Biol. 2005, 346:1221-1227.
60. Osmulski P.A., Hochstrasser M., Gaczynska M. A tetrahedral transition state at the active sites of the 20S proteasome is coupled to opening of the alpha-ring channel. Structure 2009, 17:1137-1147.
61. Park E., Rho Y.M., Koh O.J., Ahn S.W., Seong I.S., Song J.J., Bang O., Seol J.H., Wang J., Eom S.H., Chung C.H. Role of the GYVG pore motif of HslU ATPase in protein unfolding and translocation for degradation by HslV peptidase. J. Biol. Chem. 2005, 280:22892-22898.
62. Park S., Tian G., Roelofs J., Finley D. Assembly manual for the proteasome regulatory particle: the first draft. Biochem. Soc. Trans. 2010, 38:6-13.
63. Pearce M.J., Mintseris J., Ferreyra J., Gygi S.P., Darwin K.H. Ubiquitin-like protein involved in the proteasome pathway of Mycobacterium tuberculosis. Science 2008, 322:1104-1107.
64. Peth A., Besche H.C., Goldberg A.L. Ubiquitinated proteins activate the proteasome by binding to Usp14/Ubp6, which causes 20S gate opening. Mol. Cell 2009, 36:794-804.
65. Pickart C.M., Cohen R.E. Proteasomes and their kin: proteases in the machine age. Nat. Rev. Mol. Cell Biol. 2004, 5:177-187.
66. Prakash S., Tian L., Ratliff K.S., Lehotzky R.E., Matouschek A. An unstructured initiation site is required for efficient proteasome-mediated degradation. Nat. Struct. Mol. Biol. 2004, 11:830-837.
67. Prakash S., Inobe T., Hatch A.J., Matouschek A. Substrate selection by the proteasome during degradation of protein complexes. Nat. Chem. Biol. 2009, 5:29-36.
68. Rabl J., Smith D.M., Yu Y., Chang S.C., Goldberg A.L., Cheng Y. Mechanism of gate opening in the 20S proteasome by the proteasomal ATPases. Mol. Cell 2008, 30:360-368.
69. Rape M., Jentsch S. Productive RUPture: activation of transcription factors by proteasomal processing. Biochim. Biophys. Acta 2004, 1695:209-213.
70. Rechsteiner M., Hill C.P. Mobilizing the proteolytic machine: cell biological roles of proteasome activators and inhibitors. Trends Cell Biol. 2005, 15:27-33.
71. Religa T.L., Sprangers R., Kay L.E. Dynamic regulation of archaeal proteasome gate opening as studied by TROSY NMR. Science 2010, 328:98-102.
72. Rosenzweig R., Osmulski P.A., Gaczynska M., Glickman M.H. The central unit within the 19S regulatory particle of the proteasome. Nat. Struct. Mol. Biol. 2008, 15:573-580.
73. Ruschak A.M., Religa T.L., Breuer S., Witt S., Kay L.E. The proteasome antechamber maintains substrates in an unfolded state. Nature 2010, 467:868-871.
74. Sadre-Bazzaz K., Whitby F.G., Robinson H., Formosa T., Hill C.P. Structure of a Blm10 complex reveals common mechanisms for proteasome binding and gate opening. Mol. Cell 2010, 37:728-735.
75. Schmidt M., Haas W., Crosas B., Santamaria P.G., Gygi S.P., Walz T., Finley D. The HEAT repeat protein Blm10 regulates the yeast proteasome by capping the core particle. Nat. Struct. Mol. Biol. 2005, 12:294-303.
76. Seemuller E., Lupas A., Stock D., Lowe J., Huber R., Baumeister W. Proteasome from Thermoplasma acidophilum: a threonine protease. Science 1995, 268:579-582.
77. Shibatani T., Carlson E.J., Larabee F., McCormack A.L., Fruh K., Skach W.R. Global organization and function of mammalian cytosolic proteasome pools: implications for PA28 and 19S regulatory complexes. Mol. Biol. Cell 2006, 17:4962-4971.
78. Smith D.M., Kafri G., Cheng Y., Ng D., Walz T., Goldberg A.L. ATP binding to PAN or the 26S ATPases causes association with the 20S proteasome, gate opening, and translocation of unfolded proteins. Mol. Cell 2005, 20:687-698.
79. Smith D.M., Chang S.C., Park S., Finley D., Cheng Y., Goldberg A.L. Docking of the proteasomal ATPases' carboxyl termini in the 20S proteasome's alpha ring opens the gate for substrate entry. Mol. Cell 2007, 27:731-744.
80. Sousa M.C., Trame C.B., Tsuruta H., Wilbanks S.M., Reddy V.S., McKay D.B. Crystal and solution structures of an HslUV protease-chaperone complex. Cell 2000, 103:633-643.
81. Stadtmueller B.M., Ferrell K., Whitby F.G., Heroux A., Robinson H., Myszka D.G., Hill C.P. Structural models for interactions between the 20S proteasome and its PAN/19S activators. J. Biol. Chem. 2010, 285:13-17.
82. Striebel F., Hunkeler M., Summer H., Weber-Ban E. The mycobacterial Mpa-proteasome unfolds and degrades pupylated substrates by engaging Pup's N-terminus. EMBO J. 2010, 29:1262-1271.
83. Suzuki R., Moriishi K., Fukuda K., Shirakura M., Ishii K., Shoji I., Wakita T., Miyamura T., Matsuura Y., Suzuki T. Proteasomal turnover of hepatitis C virus core protein is regulated by two distinct mechanisms: a ubiquitin-dependent mechanism and a ubiquitin-independent but PA28gamma-dependent mechanism. J. Virol. 2009, 83:2389-2392.
84. Thomsen N.D., Berger J.M. Running in reverse: the structural basis for translocation polarity in hexameric helicases. Cell 2009, 139:523-534.
85. Tian L., Holmgren R.A., Matouschek A. A conserved processing mechanism regulates the activity of transcription factors Cubitus interruptus and NF-kappaB. Nat. Struct. Mol. Biol. 2005, 12:1045-1053.
86. Tomko R.J., Funakoshi M., Schneider K., Wang J., Hochstrasser M. Heterohexameric ring arrangement of the eukaryotic proteasomal ATPases: implications for proteasome structure and assembly. Mol. Cell 2010, 38:393-403.
87. Unno M., Mizushima T., Morimoto Y., Tomisugi Y., Tanaka K., Yasuoka N., Tsukihara T. The structure of the mammalian 20S proteasome at 2.75 Å resolution. Structure 2002, 10:609-618.
88. Ustrell V., Hoffman L., Pratt G., Rechsteiner M. PA200, a nuclear proteasome activator involved in DNA repair. EMBO J. 2002, 21:3516-3525.
89. Verma R., Aravind L., Oania R., McDonald W.H., Yates J.R., Koonin E.V., Deshaies R.J. Role of Rpn11 metalloprotease in deubiquitination and degradation by the 26S proteasome. Science 2002, 298:611-615.
90. Walters K.J., Lech P.J., Goh A.M., Wang Q., Howley P.M. DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a. Proc. Natl. Acad. Sci. USA 2003, 100:12694-12699.
91. Wang T., Li H., Lin G., Tang C., Li D., Nathan C., Darwin K.H. Structural insights on the Mycobacterium tuberculosis proteasomal ATPase Mpa. Structure 2009, 17:1377-1385.
92. Wang T., Darwin K.H., Li H. Binding-induced folding of prokaryotic ubiquitin-like protein on the Mycobacterium proteasomal ATPase targets substrates for degradation. Nat. Struct. Mol. Biol. 2010, 17:1352-1357.
93. Wenzel T., Baumeister W. Conformational constraints in protein degradation by the 20S proteasome. Nat. Struct. Biol. 1995, 2:199-204.
94. Whitby F.G., Masters E.I., Kramer L., Knowlton J.R., Yao Y., Wang C.C., Hill C.P. Structural basis for the activation of 20S proteasomes by 11S regulators. Nature 2000, 408:115-120.
95. Xu P., Duong D.M., Seyfried N.T., Cheng D., Xie Y., Robert J., Rush J., Hochstrasser M., Finley D., Peng J. Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell 2009, 137:133-145.
96. Yao T., Cohen R.E. A cryptic protease couples deubiquitination and degradation by the proteasome. Nature 2002, 419:403-407.
97. Yao T., Song L., Xu W., DeMartino G.N., Florens L., Swanson S.K., Washburn M.P., Conaway R.C., Conaway J.W., Cohen R.E. Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1. Nat. Cell Biol. 2006, 8:994-1002.
98. Yu Y., Smith D.M., Kim H.M., Rodriguez V., Goldberg A.L., Cheng Y. Interactions of PAN's C-termini with archaeal 20S proteasome and implications for the eukaryotic proteasome-ATPase interactions. EMBO J. 2010, 29:692-702.
99. Zhang Z., Clawson A., Realini C., Jensen C.C., Knowlton J.R., Hill C.P., Rechsteiner M. Identification of an activation region in the proteasome activator REGalpha. Proc. Natl. Acad. Sci. USA 1998, 95:2807-2811.
100. Zhang F., Hu M., Tian G., Zhang P., Finley D., Jeffrey P.D., Shi Y. Structural insights into the regulatory particle of the proteasome from Methanocaldococcus jannaschii. Mol. Cell 2009, 34:473-484.
101. Zhang F., Wu Z., Zhang P., Tian G., Finley D., Shi Y. Mechanism of substrate unfolding and translocation by the regulatory particle of the proteasome from Methanocaldococcus jannaschii. Mol. Cell 2009, 34:485-496.