Atomic resolution Cryo-EM structure of human proteasome activator PA28?
Atomic resolution Cryo-EM structure of human proteasome activator PA28?
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DOI：
10.1016/j.ijbiomac.2022.07.246
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发表时间：
2022-08-10
影响因子：
8.2
通讯作者：
Yun, Cai-Hong
中科院分区：
文献类型：
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作者：
Chen, Dan-Dan;Hao, Jia;Yun, Cai-Hong
PA 28家族蛋白酶体激活剂在调节蛋白酶体活性中起重要作用。尽管三种旁系同源物（PA 28 α、PA 28 β和PA 28 γ）在一级序列方面相似，但它们在表达模式、细胞定位以及最重要的生物学功能方面显示出显著差异。虽然PA 28 α β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，但众所周知，PA 28 γ不仅促进肽酶活性，而且促进蛋白酶体的蛋白水解活性。然而，为什么这种蛋白质具有独特的功能仍然令人费解。以前的结构研究主要集中在哺乳动物PA 28 α，PA 28 β和PA 28 α β七聚体，而迄今为止仍然缺乏原子分辨率的哺乳动物PA 28 γ的结构研究。在目前的工作中，我们确定了冷冻-EM结构的人PA 28 γ七聚体在原子分辨率，揭示有趣的独特的结构特征，可能会暗示我们理解这种蛋白酶体激活剂的功能机制。
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.