Department of Biochemistry and Biophysics, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
Hongyun Biotech Co., Ltd., Nanjing, Jiangsu 211112, China.
Int J Biol Macromol. 2022 Oct 31;219:500-507. doi: 10.1016/j.ijbiomac.2022.07.246. Epub 2022 Aug 4.
The PA28 family proteasome activators play important roles in regulating proteasome activities. Though the three paralogs (PA28α, PA28β, and PA28γ) are similar in terms of primary sequence, they show significant differences in expression pattern, cellular localization and most importantly, biological functions. While PA28αβ is responsible for promoting peptidase activity of proteasome to facilitate MHC-I antigen processing, but unable to promote protein degradation, PA28γ 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 PA28α, PA28β and PA28αβ heptamers, while structural studies on mammalian PA28γ of atomic resolution are still absent to date. In the present work, we determined the Cryo-EM structure of the human PA28γ heptamer at atomic resolution, revealing interesting unique structural features that may hint our understanding the functional mechanisms of this proteasome activator.
PA28 家族蛋白酶体激活剂在调节蛋白酶体活性方面发挥着重要作用。尽管这三个同源物（PA28α、PA28β 和 PA28γ）在一级序列上相似，但它们在表达模式、细胞定位以及最重要的生物学功能上存在显著差异。PA28αβ 负责促进蛋白酶体的肽酶活性，以促进 MHC-I 抗原加工，但不能促进蛋白质降解，而 PA28γ 不仅众所周知能促进肽酶活性，还能促进蛋白酶体的蛋白水解活性。然而，为什么这个同源物具有独特的功能仍然难以捉摸。以前的结构研究主要集中在哺乳动物的 PA28α、PA28β 和 PA28αβ 七聚体上，而目前仍缺乏关于哺乳动物 PA28γ 的原子分辨率结构研究。在本工作中，我们确定了人源 PA28γ 七聚体的冷冻电镜结构，揭示了有趣的独特结构特征，可能提示我们理解这种蛋白酶体激活剂的功能机制。
