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Rearrangement of the 16S Precursor Subunits Is Essential for the Formation of the Active 20S Proteasome

Proteasome-dependent proteolysis is essential for a number of key cellular processes and requires a sophisticated biogenesis pathway to function. Here, we have arrested the assembly process in its dynamic progression at the short-lived 16S state. Structural analysis of the 16S proteasome precursor i...

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Autors principals: Mullapudi, Srinivas, Pullan, Lee, Bishop, Ozlem T., Khalil, Hassan, Stoops, James K., Beckmann, Roland, Kloetzel, Peter M., Krüger, Elke, Penczek, Pawel A.
Format: Article
Idioma:English
Publicat: Biophysical Society 2004
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Accés en línia:https://ncbi.nlm.nih.gov/pmc/articles/PMC1304918/
https://ncbi.nlm.nih.gov/pubmed/15361411
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1529/biophysj.104.051144
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Sumari:Proteasome-dependent proteolysis is essential for a number of key cellular processes and requires a sophisticated biogenesis pathway to function. Here, we have arrested the assembly process in its dynamic progression at the short-lived 16S state. Structural analysis of the 16S proteasome precursor intermediates by electron microscopy, and single particle analysis reveals major conformational changes in the structure of the β-ring in comparison with one-half of the 20S proteasome. The individual β-subunits in the 16S precursor complex rotate with respect to their positions in the x-ray crystallographic structure of the fully assembled 20S. This rearrangement results in a movement of the catalytic residue threonine-1 from the protected location in 16S precursor complexes to a more exposed position in the 20S structure. Thereby, our findings provide a molecular explanation for the structural rearrangements necessary for the dimerization of two 16S precursor complexes and the subsequent final maturation to active 20S proteasomes.