Title:
Structure and dynamics of the 26S proteasome

Yasushi Saeki
Tokyo Metropolitan Institute of Medical Science
Laboratory of Protein Metabolism

Abstract:
The 26S proteasome is known to play pivotal roles in various cellular processes by selective breakdown of short-lived and abnormal proteins in eukaryotic cells. However, structure, mechanistic actions, and molecular dynamics of the 26S proteasome are still unclear. We recently determined the overall structure of the 26S proteasome and localization of ubiquitin receptors, Rpn10 and Rpn13, by cryoelectron microscopy. The proteasomal ubiquitin receptors are located in a distant site on the apical part of the regulatory particle of the proteasome, suggesting that this orientation allows the proteasome to trap the polyubiquitinated substrates efficiently. Currently, we focus on the molecular dynamics of the 26S proteasome. Using a live cell imaging, we found the 26S proteasome is highly mobile molecule in yeast and mammalian cultured cells, suggesting that the 26S proteasomes are not simply garbage cans of the cells. We also identified a new cytoplasmic structure of the proteasome by a screening using yeast knockout libraries. The formation of the proteasome granules may link cellular senescence.

References:
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Tanaka K, Mizushima N, and Saeki Y. Biol Chem 393, 217-234 (2012)

.Localization of the proteasomal ubiquitin receptors Rpn10 and Rpn13 by electron cryomicroscopy.
Sakata E, et al. Proc Natl Acad Sci USA 109, 1479-1484 (2012).

Multiple proteasome-interacting proteins assist the assembly of the yeast 19S regulatory particle.
Saeki Y, et al. Cell 137, 900-913 (2012).