Ecm29 fulfils quality control functions in proteasome assembly

Area of Science:

• Cellular biology
• Molecular mechanisms of protein degradation

Background:

• The proteasome is a crucial cellular machine responsible for protein degradation in eukaryotic cells.
• Its assembly involves a core particle (CP) and regulatory particles (RP), with dedicated chaperones overseeing their formation.
• Understanding the regulation of the final assembly steps is key to comprehending proteasome function.

Purpose of the Study:

• To identify proteins that regulate the final stages of regulatory particle-core particle (RP-CP) assembly in yeast.
• To elucidate the specific role of the identified protein, Ecm29, in this assembly process.

Main Methods:

• Yeast genetics to identify regulatory proteins.
• Biochemical reconstitution assays to study protein function in vitro.
• Analysis of proteasome assembly intermediates.

Main Results:

• Ecm29, a conserved HEAT-like repeat protein, was identified as a regulator of RP-CP assembly.
• Ecm29 specifically recognizes RP-CP complexes with incomplete core particle maturation.
• Ecm29 acts as a scaffold during the remodeling of immature RP-CP assemblies into functional proteasomes.

Conclusions:

• Ecm29 is essential for the integrity of RP-CP assemblies during proteasome biogenesis.
• It facilitates the maturation of the core particle by remodeling incomplete structures.
• Ecm29 is degraded and the regulatory particle dissociates upon successful completion of core particle maturation, ensuring proper proteasome function.