Structural insights on the dynamics of proteasome formation
Molecular organization in biological systems comprises elaborately programmed processes involving metastable complex formation of biomolecules. This is exemplified by the formation of the proteasome, which is one of the largest and most complicated biological supramolecular complexes. This biomolecular machinery comprises approximately 70 subunits, including structurally homologous, but functionally distinct, ones, thereby exerting versatile proteolytic functions. In eukaryotes, proteasome formation is non-autonomous and is assisted by assembly chaperones, which transiently associate with assembly intermediates, operating as molecular matchmakers and checkpoints for the correct assembly of proteasome subunits. Accumulated data also suggest that eukaryotic proteasome formation involves scrap-and-build mechanisms. However, unlike the eukaryotic proteasome subunits, the archaeal subunits show little structural divergence and spontaneously assemble into functional machinery. Nevertheless, the archaeal genomes encode homologs of eukaryotic proteasome assembly chaperones. Recent structural and functional studies of these proteins have advanced our understanding of the evolution of molecular mechanisms involved in proteasome biogenesis. This knowledge, in turn, provides a guiding principle in designing molecular machineries using protein engineering approaches and de novo synthesis of artificial molecular systems.
KeywordsAssembly chaperone Proteasome Biomolecular machinery Transient interaction
This work was supported in part by grants (JP25102001, JP25102008, and JP15H02491 to K.K.) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, by the Okazaki ORION project.
Compliance with ethical standards
Conflict of interest
Koichi Kato declares that he has no conflict of interest. Tadashi Satoh declares that he has no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
- Barrault MB, Richet N, Godard C, Murciano B, Le Tallec B, Rousseau E, Legrand P, Charbonnier JB, Le Du MH, Guérois R, Ochsenbein F, Peyroche A (2012) Dual functions of the Hsm3 protein in chaperoning and scaffolding regulatory particle subunits during the proteasome assembly. Proc Natl Acad Sci U S A 109:E1001–E1010. https://doi.org/10.1073/pnas.1116538109 CrossRefPubMedPubMedCentralGoogle Scholar
- Gerards WL, Enzlin J, Häner M, Hendriks IL, Aebi U, Bloemendal H, Boelens W (1997) The human α-type proteasomal subunit HsC8 forms a double ringlike structure, but does not assemble into proteasome-like particles with the β-type subunits HsDelta or HsBPROS26. J Biol Chem 272:10080–10086CrossRefPubMedGoogle Scholar
- Gillette TG, Kumar B, Thompson D, Slaughter CA, DeMartino GN (2008) 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 283:31813–31822. https://doi.org/10.1074/jbc.M805935200 CrossRefPubMedPubMedCentralGoogle Scholar
- Kim S, Saeki Y, Fukunaga K, Suzuki A, Takagi K, Yamane T, Tanaka K, Mizushima T, Kato K (2010) Crystal structure of yeast Rpn14, a chaperone of the 19 S regulatory particle of the proteasome. J Biol Chem 285:15159–15166. https://doi.org/10.1074/jbc.M110.104042 CrossRefPubMedPubMedCentralGoogle Scholar
- Kish-Trier E, Hill CP (2013) Structural biology of the proteasome. Annu Rev Biophys 42:29–49. https://doi.org/10.1146/annurev-biophys-083012-130417 CrossRefPubMedPubMedCentralGoogle Scholar
- Sá-Moura B, Simões AM, Fraga J, Fernandes H, Abreu IA, Botelho HM, Gomes CM, Marques AJ, Dohmen RJ, Ramos PC, Macedo-Ribeiro S (2013) Biochemical and biophysical characterization of recombinant yeast proteasome maturation factor Ump1. Comput Struct Biotechnol J 7:e201304006. https://doi.org/10.5936/csbj.201304006 CrossRefPubMedPubMedCentralGoogle Scholar
- Shajani Z, Sykes MT, Williamson JR (2011) Assembly of bacterial ribosomes. Annu Rev Biochem 80:501–526. https://doi.org/10.1146/annurev-biochem-062608-160432 CrossRefPubMedGoogle Scholar
- Stadtmueller BM, Kish-Trier E, Ferrell K, Petersen CN, Robinson H, Myszka DG, Eckert DM, Formosa T, Hill CP (2012) Structure of a proteasome Pba1–Pba2 complex: implications for proteasome assembly, activation, and biological function. J Biol Chem 287:37371–37382. https://doi.org/10.1074/jbc.M112.367003 CrossRefPubMedPubMedCentralGoogle Scholar
- Sugiyama M, Kurimoto E, Yagi H, Mori K, Fukunaga T, Hirai M, Zaccai G, Kato K (2011) Kinetic asymmetry of subunit exchange of homooligomeric protein as revealed by deuteration-assisted small-angle neutron scattering. Biophys J 101:2037–2042. https://doi.org/10.1016/j.bpj.2011.09.004 CrossRefPubMedPubMedCentralGoogle Scholar
- Sugiyama M, Yagi H, Yamaguchi T, Kumoi K, Hirai M, Oba Y, Sato N, Porcar L, Martel A, Kato K (2014) Conformational characterization of a protein complex involving intrinsically disordered protein by small-angle neutron scattering using the inverse contrast matching method: a case study of interaction between α-synuclein and PbaB tetramer as a model chaperone. J Appl Crystallogr 47:430–435CrossRefGoogle Scholar
- Takagi K, Kim S, Yukii H, Ueno M, Morishita R, Endo Y, Kato K, Tanaka K, Saeki Y, Mizushima T (2012) Structural basis for specific recognition of Rpt1p, an ATPase subunit of 26 S proteasome, by proteasome-dedicated chaperone Hsm3p. J Biol Chem 287:12172–12182. https://doi.org/10.1074/jbc.M112.345876 CrossRefPubMedPubMedCentralGoogle Scholar
- Takagi K, Saeki Y, Yashiroda H, Yagi H, Kaiho A, Murata S, Yamane T, Tanaka K, Mizushima T, Kato K (2014) Pba3–Pba4 heterodimer acts as a molecular matchmaker in proteasome α-ring formation. Biochem Biophys Res Commun 450:1110–1114. https://doi.org/10.1016/j.bbrc.2014.06.119 CrossRefPubMedGoogle Scholar
- Tomko RJ Jr, Funakoshi M, Schneider K, Wang J, Hochstrasser M (2010) Heterohexameric ring arrangement of the eukaryotic proteasomal ATPases: implications for proteasome structure and assembly. Mol Cell 38:393–403. https://doi.org/10.1016/j.molcel.2010.02.035 CrossRefPubMedPubMedCentralGoogle Scholar
- Uekusa Y, Okawa K, Yagi-Utsumi M, Serve O, Nakagawa Y, Mizushima T, Yagi H, Saeki Y, Tanaka K, Kato K (2014) Backbone 1H, 13C, and 15N assignments of yeast Ump1, an intrinsically disordered protein that functions as a proteasome assembly chaperone. Biomol NMR Assign 8:383–386. https://doi.org/10.1007/s12104-013-9523-1 CrossRefPubMedGoogle Scholar
- Yagi-Utsumi M, Sikdar A, Kozai T, Inoue R, Sugiyama M, Uchihashi T, Yagi H, Satoh T, Kato K (2017) Conversion of functionally undefined homopentameric protein PbaA into a proteasome activator by mutational modification of its C-terminal segment conformation. Protein Eng Des Sel. https://doi.org/10.1093/protein/gzx066
- Yashiroda H, Mizushima T, Okamoto K, Kameyama T, Hayashi H, Kishimoto T, Niwa SI, Kasahara M, Kurimoto E, Sakata E, Takagi K, Suzuki A, Hirano Y, Murata S, Kato K, Yamane T, Tanaka K (2008) Crystal structure of a chaperone complex that contributes to the assembly of yeast 20S proteasomes. Nat Struct Mol Biol 15:228–236. https://doi.org/10.1038/nsmb.1386 CrossRefPubMedGoogle Scholar