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Panfair Dissertation.pdf (2.87 MB)

Alternative Assembly Pathways of the 20S Proteasome and Non-canonical Complexes

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posted on 16.01.2020, 19:08 by Dilrajkaur Panfair
The 20S proteasome, a multi-subunit protease complex, present in all domains of life and some orders of bacteria, is involved in degradation of the majority of cellular proteins. Structurally, it is made of α and β subunits arranged in four heptameric rings, with inner two β-rings sandwiched between outer two α-rings. The 20S proteasome in prokaryotes usually has one type of α and one type of β subunits, whereas eukaryotes have seven distinct types of α and seven distinct types of β subunits. Unlike the highly conserved structure of proteasome, its assembly pathway is different across the domains. In archaea and eukaryotes, proteasome assembly begins with α subunit interactions leading to the α-ring formation. By contrast, bacterial proteasome assembly pathway bypasses the α-ring formation step by initiating assembly through an α and β subunit interaction first. These early interactions are not well understood due to their highly rapid and dynamic nature. This dissertation focused on understanding the early events in proteasome assembly and contributed three significant findings. First, the archaeal proteasome assembly can also begin without formation of α-rings, demonstrating the coexistence of a bacterial-like assembly pathway. Second, a novel assembly intermediate was identified in yeast, and its composition argues for the presence of a similar α-ring independent assembly pathway. Third, the assembly chaperone Pba3-Pba4 prevents the formation of high molecular weight complexes arising from spontaneous and non-productive interactions among the α subunits. These findings provide a broader understanding of proteasome biogenesis and suggest considering proteasome assembly event as a network of interactions rather than a linear pathway. The results also shed light on assembly chaperone’s contribution in increasing the efficiency of proteasome assembly by streamlining the productive interactions.

History

Degree Type

Doctor of Philosophy

Department

Biological Sciences

Campus location

Indianapolis

Advisor/Supervisor/Committee Chair

Lata Balakrishnan

Additional Committee Member 2

Andrew Kusmierczyk

Additional Committee Member 3

Stephen Randall

Additional Committee Member 4

Eric Rubenstein

Additional Committee Member 5

Gregory Anderson

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Keywords

ProteasomeAssemblyPathway

Licence

CC BY 4.0

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