7yqd
From Proteopedia
EM structure of human PA28gamma (wild-type)
Structural highlights
FunctionPSME3_HUMAN Subunit of the 11S REG-gamma (also called PA28-gamma) proteasome regulator, a doughnut-shaped homoheptamer which associates with the proteasome. 11S REG-gamma activates the trypsin-like catalytic subunit of the proteasome but inhibits the chymotrypsin-like and postglutamyl-preferring (PGPH) subunits. Facilitates the MDM2-p53/TP53 interaction which promotes ubiquitination- and MDM2-dependent proteasomal degradation of p53/TP53, limiting its accumulation and resulting in inhibited apoptosis after DNA damage. May also be involved in cell cycle regulation. Mediates CCAR2 and CHEK2-dependent SIRT1 inhibition (PubMed:25361978).[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedThe PA28 family proteasome activators play important roles in regulating proteasome activities. Though the three paralogs (PA28alpha, PA28beta, and PA28gamma) are similar in terms of primary sequence, they show significant differences in expression pattern, cellular localization and most importantly, biological functions. While PA28alphabeta is responsible for promoting peptidase activity of proteasome to facilitate MHC-I antigen processing, but unable to promote protein degradation, PA28gamma 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 PA28alpha, PA28beta and PA28alphabeta heptamers, while structural studies on mammalian PA28gamma of atomic resolution are still absent to date. In the present work, we determined the Cryo-EM structure of the human PA28gamma heptamer at atomic resolution, revealing interesting unique structural features that may hint our understanding the functional mechanisms of this proteasome activator. Atomic resolution Cryo-EM structure of human proteasome activator PA28gamma.,Chen DD, Hao J, Shen CH, Deng XM, Yun CH Int J Biol Macromol. 2022 Oct 31;219:500-507. doi: , 10.1016/j.ijbiomac.2022.07.246. Epub 2022 Aug 4. PMID:35932807[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Loading citation details.. Citations No citations found See AlsoReferences
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