Atomic resolution Cryo-EM structure of human proteasome activator PA28?

The PA28 family proteasome activators play important roles in regulating proteasome activities. Though the three paralogs (PA28 alpha, PA28 beta, and PA28 gamma) are similar in terms of primary sequence, they show significant differences in expression pattern, cellular localization and most importantly, biological functions. While PA28 alpha beta is responsible for promoting peptidase activity of proteasome to facilitate MHC-I antigen processing, but unable to promote protein degradation, PA28 gamma is well-known to not only promote peptidase activity but also proteolytic activity of proteasome. However, why this paralog has the unique function remains elusive. Previous structural studies have mainly focused on mammalian PA28 alpha, PA28 beta and PA28 alpha beta heptamers, while structural studies on mammalian PA28 gamma of atomic resolution are still absent to date. In the present work, we determined the Cryo-EM structure of the human PA28 gamma heptamer at atomic resolution, revealing interesting unique structural features that may hint our understanding the functional mechanisms of this proteasome activator.

Automated summary

The PA28 family proteasome activators play crucial roles in regulating proteasome activities. However, the paralogs, PA28 alpha, PA28 beta, and PA28 gamma, have distinct expression patterns, cellular localizations, and biological functions. This study provides an atomic resolution Cryo-EM structure of the human PA28 gamma heptamer, revealing unique structural features that may contribute to our understanding of its functional mechanisms.