ATP Binding and ATP Hydrolysis Play Distinct Roles in the Function of 26S Proteasome

Chang Wei Liu, Xiaohua Li, David Thompson, Kerry Wooding, Tsui ling Chang, Zhanyun Tang, Hongtao Yu, Philip J. Thomas, George N. DeMartino

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

The 26S proteasome degrades polyubiquitinated proteins by an energy-dependent mechanism. Here we define multiple roles for ATP in 26S proteasome function. ATP binding is necessary and sufficient for assembly of 26S proteasome from 20S proteasome and PA700/19S subcomplexes and for proteasome activation. Proteasome assembly and activation may require distinct ATP binding events. The 26S proteasome degrades nonubiquitylated, unstructured proteins without ATP hydrolysis, indicating that substrate translocation per se does not require the energy of hydrolysis. Nonubiquitylated folded proteins and certain polyubiquitylated folded proteins were refractory to proteolysis. The latter were deubiquitylated by an ATP-independent mechanism. Other folded as well as unstructured polyubiquitylated proteins required ATP hydrolysis for proteolysis and deubiquitylation. Thus, ATP hydrolysis is not used solely for substrate unfolding. These results indicate that 26S proteasome-catalyzed degradation of polyubiquitylated proteins involves mechanistic coupling of several processes and that such coupling imposes an energy requirement not apparent for any isolated process.

Original languageEnglish (US)
Pages (from-to)39-50
Number of pages12
JournalMolecular Cell
Volume24
Issue number1
DOIs
StatePublished - Oct 6 2006

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Hydrolysis
Adenosine Triphosphate
Proteasome Endopeptidase Complex
Proteolysis
Proteins
Intrinsically Disordered Proteins
ATP dependent 26S protease

Keywords

  • PROTEINS

ASJC Scopus subject areas

  • Molecular Biology

Cite this

ATP Binding and ATP Hydrolysis Play Distinct Roles in the Function of 26S Proteasome. / Liu, Chang Wei; Li, Xiaohua; Thompson, David; Wooding, Kerry; Chang, Tsui ling; Tang, Zhanyun; Yu, Hongtao; Thomas, Philip J.; DeMartino, George N.

In: Molecular Cell, Vol. 24, No. 1, 06.10.2006, p. 39-50.

Research output: Contribution to journalArticle

Liu, Chang Wei ; Li, Xiaohua ; Thompson, David ; Wooding, Kerry ; Chang, Tsui ling ; Tang, Zhanyun ; Yu, Hongtao ; Thomas, Philip J. ; DeMartino, George N. / ATP Binding and ATP Hydrolysis Play Distinct Roles in the Function of 26S Proteasome. In: Molecular Cell. 2006 ; Vol. 24, No. 1. pp. 39-50.
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