title: 20S proteasome prevents aggregation of heat-denatured proteins without PA700 regulatory subcomplex like a molecular chaperone.
abstract: The eukaryotic 20S proteasome is the multifunctional catalytic core of the 26S proteasome, which plays a central role in intracellular protein degradation. Association of the 20S core with a regulatory subcomplex, termed PA700 (also known as the 19S cap), forms the 26S proteasome, which degrades ubiquitinated and nonubiquitinated proteins through an ATP-dependent process. Although proteolytic assistance by this regulatory particle is a general feature of proteasome-dependent turnover, the 20S proteasome itself can degrade some proteins directly, bypassing ubiquitination and PA700, as an alternative mechanism in vitro. The mechanism underlying this pathway is based on the ability of the 20S proteasome to recognize partially unfolded proteins. Here we show that the 20S proteasome recognizes the heat-denatured forms of model proteins such as citrate synthase, malate dehydrogenase. and glyceraldehydes-3-phosphate dehydrogenase, and prevents their aggregation in vitro. This process was not followed by the refolding of these denatured substrates into their native states, whereas PA700 or the 26S proteasome generally promotes their reactivation. These results indicate that the 20S proteasome might play a role in maintaining denatured and misfolded substrates in a soluble state, thereby facilitating their refolding or degradation.
authors.affiliation: Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Tokushima 770-8503, Japan.
authors.forename: Mihiro
authors.initials: M
authors.lastname: Yano
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Koumoto
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kanesaki
authors.forename: Xueji
authors.initials: X
authors.lastname: Wu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kido
mesh_terms: D000818:Animals; D002950:Citrate (si)-Synthase / Q000378:metabolism; D019286:Endopeptidase K / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000737:chemistry / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000378:metabolism; D011489:Protein Denaturation / Q000502:physiology; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D013997:Time Factors
chemical_list: D018832:Molecular Chaperones; C085834:PA700 proteasome activator; D011506:Proteins; D008156:Luciferases; D002950:Citrate (si)-Synthase; D019286:Endopeptidase K; D046988:Proteasome Endopeptidase Complex