Reconfiguration of the Proteasome During Chaperone-mediated Assembly

Overview

Journal Nature

Specialty Science

Date 2013 May 7

PMID 23644457

Citations 47

Authors

Soyeon Park

Xueming Li

Ho Min Kim

Chingakham Ranjit Singh

Geng Tian

Martin A Hoyt

Scott Lovell

Kevin P Battaile

Michal Zolkiewski

Philip Coffino

Jeroen Roelofs

Yifan Cheng

Daniel Finley

Affiliations

Soon will be listed here.

Abstract

The proteasomal ATPase ring, comprising Rpt1-Rpt6, associates with the heptameric α-ring of the proteasome core particle (CP) in the mature proteasome, with the Rpt carboxy-terminal tails inserting into pockets of the α-ring. Rpt ring assembly is mediated by four chaperones, each binding a distinct Rpt subunit. Here we report that the base subassembly of the Saccharomyces cerevisiae proteasome, which includes the Rpt ring, forms a high-affinity complex with the CP. This complex is subject to active dissociation by the chaperones Hsm3, Nas6 and Rpn14. Chaperone-mediated dissociation was abrogated by a non-hydrolysable ATP analogue, indicating that chaperone action is coupled to nucleotide hydrolysis by the Rpt ring. Unexpectedly, synthetic Rpt tail peptides bound α-pockets with poor specificity, except for Rpt6, which uniquely bound the α2/α3-pocket. Although the Rpt6 tail is not visualized within an α-pocket in mature proteasomes, it inserts into the α2/α3-pocket in the base-CP complex and is important for complex formation. Thus, the Rpt-CP interface is reconfigured when the lid complex joins the nascent proteasome to form the mature holoenzyme.

Citing Articles

Wiggle and Shake: Managing and Exploiting Conformational Dynamics during Proteasome Biogenesis.

Betancourt D, Lawal T, Tomko Jr R Biomolecules. 2023; 13(8).

PMID: 37627288 PMC: 10452565. DOI: 10.3390/biom13081223.

A hierarchical assembly pathway directs the unique subunit arrangement of TRiC/CCT.

Betancourt Moreira K, Collier M, Leitner A, Li K, Lachapel I, McCarthy F Mol Cell. 2023; 83(17):3123-3139.e8.

PMID: 37625406 PMC: 11209756. DOI: 10.1016/j.molcel.2023.07.031.

Substrate-specific effects of natural genetic variation on proteasome activity.

Collins M, Avery R, Albert F PLoS Genet. 2023; 19(5):e1010734.

PMID: 37126494 PMC: 10174532. DOI: 10.1371/journal.pgen.1010734.

Assembly chaperone Nas6 selectively destabilizes 26S proteasomes with defective regulatory particle-core particle interfaces.

Warnock J, Jobin G, Kumar S, Tomko Jr R J Biol Chem. 2023; 299(2):102894.

PMID: 36634850 PMC: 9943895. DOI: 10.1016/j.jbc.2023.102894.

Assembly checkpoint of the proteasome regulatory particle is activated by coordinated actions of proteasomal ATPase chaperones.

Nahar A, Sokolova V, Sekaran S, Orth J, Park S Cell Rep. 2022; 39(10):110918.

PMID: 35675778 PMC: 9214829. DOI: 10.1016/j.celrep.2022.110918.

References

Forster A, Masters E, Whitby F, Robinson H, Hill C . The 1.9 A structure of a proteasome-11S activator complex and implications for proteasome-PAN/PA700 interactions. Mol Cell. 2005; 18(5):589-99. DOI: 10.1016/j.molcel.2005.04.016. View

Smith D, Kafri G, Cheng Y, Ng D, Walz T, Goldberg A . 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(5):687-98. DOI: 10.1016/j.molcel.2005.10.019. View

Lander G, Estrin E, Matyskiela M, Bashore C, Nogales E, Martin A . Complete subunit architecture of the proteasome regulatory particle. Nature. 2012; 482(7384):186-91. PMC: 3285539. DOI: 10.1038/nature10774. View

Funakoshi M, Tomko Jr R, Kobayashi H, Hochstrasser M . Multiple assembly chaperones govern biogenesis of the proteasome regulatory particle base. Cell. 2009; 137(5):887-99. PMC: 2718848. DOI: 10.1016/j.cell.2009.04.061. View

Roelofs J, Park S, Haas W, Tian G, McAllister F, Huo Y . Chaperone-mediated pathway of proteasome regulatory particle assembly. Nature. 2009; 459(7248):861-5. PMC: 2727592. DOI: 10.1038/nature08063. View

Thompson D, Hakala K, DeMartino G . Subcomplexes of PA700, the 19 S regulator of the 26 S proteasome, reveal relative roles of AAA subunits in 26 S proteasome assembly and activation and ATPase activity. J Biol Chem. 2009; 284(37):24891-903. PMC: 2757192. DOI: 10.1074/jbc.M109.023218. View

Le Tallec B, Barrault M, Guerois R, Carre T, Peyroche A . Hsm3/S5b participates in the assembly pathway of the 19S regulatory particle of the proteasome. Mol Cell. 2009; 33(3):389-99. DOI: 10.1016/j.molcel.2009.01.010. View

Park S, Kim W, Tian G, Gygi S, Finley D . Structural defects in the regulatory particle-core particle interface of the proteasome induce a novel proteasome stress response. J Biol Chem. 2011; 286(42):36652-66. PMC: 3196138. DOI: 10.1074/jbc.M111.285924. View

Smith D, Fraga H, Reis C, Kafri G, Goldberg A . ATP binds to proteasomal ATPases in pairs with distinct functional effects, implying an ordered reaction cycle. Cell. 2011; 144(4):526-38. PMC: 3063399. DOI: 10.1016/j.cell.2011.02.005. View

10.

Kish-Trier E, Hill C . Structural biology of the proteasome. Annu Rev Biophys. 2013; 42:29-49. PMC: 4878838. DOI: 10.1146/annurev-biophys-083012-130417. View

11.

Barrault M, Richet N, Godard C, Murciano B, Le Tallec B, Rousseau E . Dual functions of the Hsm3 protein in chaperoning and scaffolding regulatory particle subunits during the proteasome assembly. Proc Natl Acad Sci U S A. 2012; 109(17):E1001-10. PMC: 3340050. DOI: 10.1073/pnas.1116538109. View

12.

Kusmierczyk A, Kunjappu M, Funakoshi M, Hochstrasser M . A multimeric assembly factor controls the formation of alternative 20S proteasomes. Nat Struct Mol Biol. 2008; 15(3):237-44. DOI: 10.1038/nsmb.1389. View

13.

Saeki Y, Toh-E A, Kudo T, Kawamura H, Tanaka K . Multiple proteasome-interacting proteins assist the assembly of the yeast 19S regulatory particle. Cell. 2009; 137(5):900-13. DOI: 10.1016/j.cell.2009.05.005. View

14.

Tian G, Park S, Lee M, Huck B, McAllister F, Hill C . An asymmetric interface between the regulatory and core particles of the proteasome. Nat Struct Mol Biol. 2011; 18(11):1259-67. PMC: 3210322. DOI: 10.1038/nsmb.2147. View

15.

Lasker K, Forster F, Bohn S, Walzthoeni T, Villa E, Unverdorben P . Molecular architecture of the 26S proteasome holocomplex determined by an integrative approach. Proc Natl Acad Sci U S A. 2012; 109(5):1380-7. PMC: 3277140. DOI: 10.1073/pnas.1120559109. View

16.

Smith D, Chang S, Park S, Finley D, Cheng Y, Goldberg A . Docking of the proteasomal ATPases' carboxyl termini in the 20S proteasome's alpha ring opens the gate for substrate entry. Mol Cell. 2007; 27(5):731-44. PMC: 2083707. DOI: 10.1016/j.molcel.2007.06.033. View

17.

Kaneko T, Hamazaki J, Iemura S, Sasaki K, Furuyama K, Natsume T . Assembly pathway of the Mammalian proteasome base subcomplex is mediated by multiple specific chaperones. Cell. 2009; 137(5):914-25. DOI: 10.1016/j.cell.2009.05.008. View

18.

Takagi K, Kim S, Yukii H, Ueno M, Morishita R, Endo Y . Structural basis for specific recognition of Rpt1p, an ATPase subunit of 26 S proteasome, by proteasome-dedicated chaperone Hsm3p. J Biol Chem. 2012; 287(15):12172-82. PMC: 3320968. DOI: 10.1074/jbc.M112.345876. View

19.

Tomko Jr R, 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(3):393-403. PMC: 2879271. DOI: 10.1016/j.molcel.2010.02.035. View

20.

Ghaemmaghami S, Huh W, Bower K, Howson R, Belle A, Dephoure N . Global analysis of protein expression in yeast. Nature. 2003; 425(6959):737-41. DOI: 10.1038/nature02046. View