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基本情報
登録情報 | データベース: PDB / ID: 7drw | ||||||
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タイトル | Bovine 20S immunoproteasome in complex with two human PA28alpha-beta activators | ||||||
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![]() | HYDROLASE / proteasome / immunoproteasome / bovine spleen / PA28 | ||||||
機能・相同性 | ![]() Cross-presentation of soluble exogenous antigens (endosomes) / Regulation of ornithine decarboxylase (ODC) / proteasome activator complex / spermatoproteasome complex / Activation of NF-kappaB in B cells / 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 / SCF(Skp2)-mediated degradation of p27/p21 ...Cross-presentation of soluble exogenous antigens (endosomes) / Regulation of ornithine decarboxylase (ODC) / proteasome activator complex / spermatoproteasome complex / Activation of NF-kappaB in B cells / 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 / SCF(Skp2)-mediated degradation of p27/p21 / FCERI mediated NF-kB activation / Autodegradation of the E3 ubiquitin ligase COP1 / Asymmetric localization of PCP proteins / Degradation of AXIN / Degradation of DVL / Hedgehog ligand biogenesis / Dectin-1 mediated noncanonical NF-kB signaling / CLEC7A (Dectin-1) signaling / Degradation of GLI1 by the proteasome / Hedgehog 'on' state / TNFR2 non-canonical NF-kB pathway / NIK-->noncanonical NF-kB signaling / Assembly of the pre-replicative complex / Orc1 removal from chromatin / CDK-mediated phosphorylation and removal of Cdc6 / G2/M Checkpoints / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Ubiquitin-dependent degradation of Cyclin D / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Regulation of RUNX2 expression and activity / Regulation of RUNX3 expression and activity / Regulation of PTEN stability and activity / Interleukin-1 signaling / KEAP1-NFE2L2 pathway / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / Degradation of beta-catenin by the destruction complex / Neddylation / antigen processing and presentation of exogenous antigen / Antigen processing: Ubiquitination & Proteasome degradation / 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 / Separation of Sister Chromatids / AUF1 (hnRNP D0) binds and destabilizes mRNA / GLI3 is processed to GLI3R by the proteasome / MAPK6/MAPK4 signaling / proteasome core complex / Regulation of ornithine decarboxylase (ODC) / Cross-presentation of soluble exogenous antigens (endosomes) / Neutrophil degranulation / Somitogenesis / immune system process / fat cell differentiation / regulation of G1/S transition of mitotic cell cycle / antigen processing and presentation / endopeptidase activator activity / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / proteasome core complex, alpha-subunit complex / threonine-type endopeptidase activity / regulation of proteasomal protein catabolic process / negative regulation of inflammatory response to antigenic stimulus / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / proteasome complex / Regulation of activated PAK-2p34 by proteasome mediated degradation / ciliary basal body / Autodegradation of Cdh1 by Cdh1:APC/C / proteolysis involved in protein catabolic process / APC/C:Cdc20 mediated degradation of Securin / Asymmetric localization of PCP proteins / SCF-beta-TrCP mediated degradation of Emi1 / AUF1 (hnRNP D0) binds and destabilizes mRNA / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / TNFR2 non-canonical NF-kB pathway / Assembly of the pre-replicative complex / Vpu mediated degradation of CD4 / Degradation of DVL / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Dectin-1 mediated noncanonical NF-kB signaling / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Hh mutants are degraded by ERAD / lipopolysaccharide binding / Degradation of AXIN / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / Defective CFTR causes cystic fibrosis / Hedgehog ligand biogenesis / Negative regulation of NOTCH4 signaling / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / G2/M Checkpoints / Vif-mediated degradation of APOBEC3G / Autodegradation of the E3 ubiquitin ligase COP1 / Hedgehog 'on' state / Regulation of RUNX3 expression and activity / Degradation of GLI2 by the proteasome 類似検索 - 分子機能 | ||||||
生物種 | ![]() ![]() ![]() | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.2 Å | ||||||
![]() | Cong, Y. / Xu, C. | ||||||
資金援助 | ![]()
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![]() | ![]() 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. | ||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 1.5 MB | 表示 | ![]() |
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PDB形式 | ![]() | 1.3 MB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
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-検証レポート
文書・要旨 | ![]() | 1.1 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.1 MB | 表示 | |
XML形式データ | ![]() | 195.8 KB | 表示 | |
CIF形式データ | ![]() | 308.3 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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要素
-Proteasome subunit alpha type- ... , 7種, 14分子 AfBhCjDPERFbGd
#1: タンパク質 | 分子量: 27432.459 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #2: タンパク質 | 分子量: 25927.535 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #3: タンパク質 | 分子量: 29525.842 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #4: タンパク質 | 分子量: 27911.912 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #5: タンパク質 | 分子量: 26435.977 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #6: タンパク質 | 分子量: 29625.654 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #7: タンパク質 | 分子量: 28441.197 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() |
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-Proteasome activator complex subunit ... , 2種, 14分子 HKMOcgIJLNQaei
#8: タンパク質 | 分子量: 27398.600 Da / 分子数: 6 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #9: タンパク質 | 分子量: 28768.141 Da / 分子数: 8 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
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-Proteasome subunit beta type- ... , 7種, 14分子 kSlTmUnVWZX1Y2
#10: タンパク質 | 分子量: 23016.947 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #11: タンパク質 | 分子量: 22924.309 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #12: タンパク質 | 分子量: 26278.059 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #13: タンパク質 | 分子量: 29057.018 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #14: タンパク質 | 分子量: 23427.428 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #15: タンパク質 | 分子量: 29128.318 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() #16: タンパク質 | 分子量: 30304.332 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) ![]() ![]() |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 | 名称: 20S immunoproteasome purified from bovine spleen / タイプ: COMPLEX / Entity ID: all / 由来: NATURAL |
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由来(天然) | 生物種: ![]() ![]() |
緩衝液 | pH: 7.4 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 38 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
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解析
ソフトウェア | 名称: PHENIX / バージョン: 1.10.1_2155: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 4.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 24657 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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