Proteasome activator 200: the heat is on

Area of Science:

• Cell Biology
• Molecular Biology
• Structural Biology

Background:

• Proteasomes are essential for regulated protein degradation in eukaryotic cells.
• The 20S core particle (CP) and 26S holoenzyme are key proteasome forms.
• PA200 is a proteasome activator with roles in spermatogenesis, DNA repair, and mitochondrial inheritance.

Purpose of the Study:

• To elucidate the structural basis of PA200 (Blm10) interaction with the 20S proteasome core particle (CP).
• To understand how PA200 regulates proteasome activity and potentially influences the 26S proteasome.

Main Methods:

• X-ray crystallography was used to determine the three-dimensional molecular structure of the Blm10-CP complex.
• Structural analysis focused on the interaction interface and conformational changes induced by Blm10.

Main Results:

• The carboxy terminus of Blm10 inserts into a pocket on the CP surface.
• HEAT-like repeats of Blm10 form an asymmetric solenoid, stabilizing a partially open CP conformation.
• This structure provides a model for how PA200 activates the CP and interacts with the 19S regulatory particle (RP).

Conclusions:

• PA200/Blm10 acts as a structural regulator of the 20S proteasome.
• The determined structure offers insights into proteasome activation and the assembly of hybrid proteasome complexes.
• Understanding PA200's mechanism is crucial for comprehending proteasome function and regulation.