Dissertation/Thesis Abstract

20S Proteasome Assembly: Alternative Pathways and Complexes
by Hammack, Lindsay J., Ph.D., Purdue University, 2017, 128; 10211960
Abstract (Summary)

The ubiquitin-proteasome system is responsible for the targeted degradation of proteins within the cell. The 26S proteasome, which is the protease of this system, is a high molecular weight complex consisting of 33 subunits that arrange to form two smaller complexes the 19S regulatory particle (RP) and the 20S core particle (CP). The 19S RP can bind one or both ends of the 20S CP and is responsible for recognizing the ubiquitinated substrates. After recognition, the 19S RP will subsequently deubiquitinate, unfold, and translocate the substrates into the proteolytic 20S CP. The 20S CP consists of seven unique α and seven unique β subunits that arrange into four stacked rings, with two α rings capping two β rings. Assembly of the α(1-7)β(1-7)β(1-7)α(1-7) structure begins with the formation of an α ring and proceeds through specific assembly intermediates. This process is assisted by assembly chaperone proteins that promote on pathway interactions to efficiently construct the 20S CP. In this dissertation, three new findings are described which further characterize the proteasome assembly pathway. First, novel non-canonical complexes comprised of proteasome subunit α4 were identified in vivo, revealing proteasome subunits can assemble into complexes outside of the proteasome. Second, Hsp70 proteins, Ssa1/2, were shown to assist in the assembly of 20S CPs, adding to the growing list of proteins guiding proteasome assembly. Third, a novel complex was identified which is believed to represent a new proteasome assembly intermediate.

Indexing (document details)
Advisor: Kusmierczyk, Andrew R.
Commitee: Mosley, Amber L., Randall, Stephen, Baucum, A. J.
School: Purdue University
Department: Biological Sciences
School Location: United States -- Indiana
Source: DAI-B 81/7(E), Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Biology, Biochemistry
Keywords: Heat shock protein, Hsp70, Molecular chaperone, Proteasomes, Protein assembly
Publication Number: 10211960
ISBN: 9781392667774
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