Protein unfolding and degradation by the AAA+ Lon protease

Eyal Gur, Marina Vishkautzan, Robert T. Sauer

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

AAA+ proteases employ a hexameric ring that harnesses the energy of ATP binding and hydrolysis to unfold native substrates and translocate the unfolded polypeptide into an interior compartment for degradation. What determines the ability of different AAA+ enzymes to unfold and thus degrade different native protein substrates is currently uncertain. Here, we explore the ability of the E. coli Lon protease to unfold and degrade model protein substrates beginning at N-terminal, C-terminal, or internal degrons. Lon has historically been viewed as a weak unfoldase, but we demonstrate robust and processive unfolding/degradation of some substrates with very stable protein domains, including mDHFR and titin I27. For some native substrates, Lon is a more active unfoldase than related AAA+ proteases, including ClpXP and ClpAP. For other substrates, this relationship is reversed. Thus, unfolding activity does not appear to be an intrinsic enzymatic property. Instead, it depends on the specific protease and substrate, suggesting that evolution has diversified rather than optimized the protein unfolding activities of different AAA+ proteases. Published by Wiley-Blackwell.

Original languageEnglish
Pages (from-to)268-278
Number of pages11
JournalProtein Science
Volume21
Issue number2
DOIs
StatePublished - 1 Feb 2012

Keywords

  • AAA+ proteolytic machine
  • ATP-dependent denaturation
  • Protein unfolding
  • Ranking unfolding power

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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