Regulation of ornithine decarboxylase (ODC) / Proteasome assembly / Cross-presentation of soluble exogenous antigens (endosomes) / proteasome activator complex / spermatoproteasome complex / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Autodegradation of the E3 ubiquitin ligase COP1 ...Regulation of ornithine decarboxylase (ODC) / Proteasome assembly / Cross-presentation of soluble exogenous antigens (endosomes) / proteasome activator complex / spermatoproteasome complex / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Autodegradation of the E3 ubiquitin ligase COP1 / Asymmetric localization of PCP proteins / Degradation of AXIN / Degradation of DVL / Hedgehog ligand biogenesis / Hedgehog 'on' state / TNFR2 non-canonical NF-kB pathway / Assembly of the pre-replicative complex / CDK-mediated phosphorylation and removal of Cdc6 / G2/M Checkpoints / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Ubiquitin-dependent degradation of Cyclin D / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Regulation of RUNX3 expression and activity / Regulation of PTEN stability and activity / KEAP1-NFE2L2 pathway / Activation of NF-kappaB in B cells / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / SCF(Skp2)-mediated degradation of p27/p21 / FCERI mediated NF-kB activation / Dectin-1 mediated noncanonical NF-kB signaling / CLEC7A (Dectin-1) signaling / Degradation of GLI1 by the proteasome / NIK-->noncanonical NF-kB signaling / Orc1 removal from chromatin / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / Regulation of RUNX2 expression and activity / Interleukin-1 signaling / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Degradation of beta-catenin by the destruction complex / Neddylation / Antigen processing: Ubiquitination & Proteasome degradation / antigen processing and presentation of exogenous antigen / UCH proteinases / ABC-family proteins mediated transport / Ub-specific processing proteases / Downstream TCR signaling / The role of GTSE1 in G2/M progression after G2 checkpoint / AUF1 (hnRNP D0) binds and destabilizes mRNA / Separation of Sister Chromatids / MAPK6/MAPK4 signaling / GLI3 is processed to GLI3R by the proteasome / Neutrophil degranulation / Proteasome assembly / proteasome core complex / fat cell differentiation / regulation of G1/S transition of mitotic cell cycle / immune system process / endopeptidase activator activity / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / threonine-type endopeptidase activity / proteasome core complex, alpha-subunit complex / regulation of proteasomal protein catabolic process / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / proteasome complex / proteolysis involved in protein catabolic process / lipopolysaccharide binding / negative regulation of inflammatory response to antigenic stimulus / P-body / endopeptidase activity / proteasome-mediated ubiquitin-dependent protein catabolic process / ciliary basal body / mitochondrion / extracellular exosome / nucleoplasm / identical protein binding / nucleus / membrane / cytosol / cytoplasm 類似検索 - 分子機能
ジャーナル: Nat Commun / 年: 2021 タイトル: Cryo-EM of mammalian PA28αβ-iCP immunoproteasome reveals a distinct mechanism of proteasome activation by PA28αβ. 著者: Jinhuan Chen / Yifan Wang / Cong Xu / Kaijian Chen / Qiaoyu Zhao / Shutian Wang / Yue Yin / Chao Peng / Zhanyu Ding / Yao Cong / 要旨: The proteasome activator PA28αβ affects MHC class I antigen presentation by associating with immunoproteasome core particles (iCPs). However, due to the lack of a mammalian PA28αβ-iCP structure, ...The proteasome activator PA28αβ affects MHC class I antigen presentation by associating with immunoproteasome core particles (iCPs). However, due to the lack of a mammalian PA28αβ-iCP structure, how PA28αβ regulates proteasome remains elusive. Here we present the complete architectures of the mammalian PA28αβ-iCP immunoproteasome and free iCP at near atomic-resolution by cryo-EM, and determine the spatial arrangement between PA28αβ and iCP through XL-MS. Our structures reveal a slight leaning of PA28αβ towards the α3-α4 side of iCP, disturbing the allosteric network of the gatekeeper α2/3/4 subunits, resulting in a partial open iCP gate. We find that the binding and activation mechanism of iCP by PA28αβ is distinct from those of constitutive CP by the homoheptameric TbPA26 or PfPA28. Our study sheds lights on the mechanism of enzymatic activity stimulation of immunoproteasome and suggests that PA28αβ-iCP has experienced profound remodeling during evolution to achieve its current level of function in immune response.