<a>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.</a>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/7427822 |
| Date | 16 January 2020 |
| Creators | Dilrajkaur Panfair (5931107) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/Alternative_Assembly_Pathways_of_the_20S_Proteasome_and_Non-canonical_Complexes/7427822 |
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