登録情報 データベース : EMDB / ID : EMD-22259 構造の表示 ダウンロードとリンクタイトル Human 20S proteasome bound to an engineered 11S (PA26) activator マップデータSharpened and masked 詳細 試料複合体 : PA26-bound proteasome複合体 : Proteasome複合体 : mutant PA26 詳細 キーワード 11S-bound / 20S proteasome / HYDROLASE機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
proteasome activator complex / purine ribonucleoside triphosphate binding / Regulation of ornithine decarboxylase (ODC) / Proteasome assembly / Cross-presentation of soluble exogenous antigens (endosomes) / proteasome core complex / Somitogenesis / myofibril / immune system process / NF-kappaB binding ... proteasome activator complex / purine ribonucleoside triphosphate binding / Regulation of ornithine decarboxylase (ODC) / Proteasome assembly / Cross-presentation of soluble exogenous antigens (endosomes) / proteasome core complex / Somitogenesis / myofibril / immune system process / NF-kappaB binding / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / proteasome assembly / threonine-type endopeptidase activity / proteasome core complex, alpha-subunit complex / regulation of proteasomal protein catabolic process / proteasome complex / proteolysis involved in protein catabolic process / sarcomere / Regulation of activated PAK-2p34 by proteasome mediated degradation / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / Asymmetric localization of PCP proteins / Ubiquitin-dependent degradation of Cyclin D / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / TNFR2 non-canonical NF-kB pathway / AUF1 (hnRNP D0) binds and destabilizes mRNA / Vpu mediated degradation of CD4 / Assembly of the pre-replicative complex / Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A / Degradation of DVL / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Dectin-1 mediated noncanonical NF-kB signaling / lipopolysaccharide binding / Degradation of AXIN / Hh mutants are degraded by ERAD / negative regulation of inflammatory response to antigenic stimulus / Activation of NF-kappaB in B cells / P-body / Degradation of GLI1 by the proteasome / Hedgehog ligand biogenesis / G2/M Checkpoints / Defective CFTR causes cystic fibrosis / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Autodegradation of the E3 ubiquitin ligase COP1 / Negative regulation of NOTCH4 signaling / Vif-mediated degradation of APOBEC3G / Regulation of RUNX3 expression and activity / Hedgehog 'on' state / Degradation of GLI2 by the proteasome / GLI3 is processed to GLI3R by the proteasome / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / : / MAPK6/MAPK4 signaling / Degradation of beta-catenin by the destruction complex / response to virus / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / ABC-family proteins mediated transport / CDK-mediated phosphorylation and removal of Cdc6 / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / Regulation of expression of SLITs and ROBOs / FCERI mediated NF-kB activation / nuclear matrix / Regulation of PTEN stability and activity / Interleukin-1 signaling / Orc1 removal from chromatin / Regulation of RAS by GAPs / positive regulation of NF-kappaB transcription factor activity / Regulation of RUNX2 expression and activity / Separation of Sister Chromatids / The role of GTSE1 in G2/M progression after G2 checkpoint / UCH proteinases / KEAP1-NFE2L2 pathway / Antigen processing: Ubiquitination & Proteasome degradation / Downstream TCR signaling / peptidase activity / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Neddylation / ER-Phagosome pathway / regulation of inflammatory response / secretory granule lumen / endopeptidase activity / response to oxidative stress / proteasome-mediated ubiquitin-dependent protein catabolic process / ficolin-1-rich granule lumen / Ub-specific processing proteases / ciliary basal body / nuclear body / cilium / ribosome / cadherin binding / intracellular membrane-bounded organelle / centrosome / ubiquitin protein ligase binding / Neutrophil degranulation / mitochondrion / proteolysis 類似検索 - 分子機能 Proteasome activator PA28, C-terminal domain / Proteasome activator superfamily / Proteasome activator PA28, C-terminal domain superfamily / Proteasome activator PA28, C-terminal / Proteasome subunit alpha 1 / Proteasome beta subunit, C-terminal / Proteasome beta subunits C terminal / Proteasome subunit beta 4 / Proteasome subunit beta 2 / Proteasome beta 3 subunit ... Proteasome activator PA28, C-terminal domain / Proteasome activator superfamily / Proteasome activator PA28, C-terminal domain superfamily / Proteasome activator PA28, C-terminal / Proteasome subunit alpha 1 / Proteasome beta subunit, C-terminal / Proteasome beta subunits C terminal / Proteasome subunit beta 4 / Proteasome subunit beta 2 / Proteasome beta 3 subunit / Proteasome subunit alpha6 / Proteasome subunit alpha5 / Proteasome beta-type subunits signature. / Peptidase T1A, proteasome beta-subunit / Proteasome beta-type subunit, conserved site / Proteasome subunit A N-terminal signature / Proteasome alpha-type subunits signature. / Proteasome alpha-subunit, N-terminal domain / Proteasome subunit A N-terminal signature Add an annotation / Proteasome B-type subunit / Proteasome beta-type subunit profile. / : / Proteasome alpha-type subunit / Proteasome alpha-type subunit profile. / Proteasome subunit / Proteasome, subunit alpha/beta / Nucleophile aminohydrolases, N-terminal 類似検索 - ドメイン・相同性 Proteasome subunit alpha type-7 / Proteasome subunit beta type-1 / Proteasome subunit alpha type-1 / Proteasome subunit alpha type-2 / Proteasome subunit alpha type-3 / Proteasome subunit alpha type-4 / Proteasome subunit alpha type-5 / Proteasome subunit beta type-4 / Proteasome subunit beta type-6 / Proteasome subunit beta type-5 ... Proteasome subunit alpha type-7 / Proteasome subunit beta type-1 / Proteasome subunit alpha type-1 / Proteasome subunit alpha type-2 / Proteasome subunit alpha type-3 / Proteasome subunit alpha type-4 / Proteasome subunit alpha type-5 / Proteasome subunit beta type-4 / Proteasome subunit beta type-6 / Proteasome subunit beta type-5 / Proteasome subunit beta type-3 / Proteasome subunit beta type-2 / Proteasome subunit alpha type-6 / Proteasome subunit beta type-7 / Proteasome activator protein PA26 類似検索 - 構成要素生物種 Homo sapiens (ヒト) / Trypanosoma brucei (トリパノソーマ)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.0 Å 詳細 データ登録者de la Pena AH / Opoku-Nsiah KA / Williams SK / Chopra N / Sali A / Gestwicki JE / Lander GC 資金援助 米国, 2件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) DP2-EB020402 米国 American Cancer Society 132279-PF-18-189-01- DMC 米国
引用ジャーナル : Nat Commun / 年 : 2022タイトル : The YΦ motif defines the structure-activity relationships of human 20S proteasome activators.著者 : Kwadwo A Opoku-Nsiah / Andres H de la Pena / Sarah K Williams / Nikita Chopra / Andrej Sali / Gabriel C Lander / Jason E Gestwicki / 要旨 : The 20S proteasome (20S) facilitates turnover of most eukaryotic proteins. Substrate entry into the 20S first requires opening of gating loops through binding of HbYX motifs that are present at the C- ... The 20S proteasome (20S) facilitates turnover of most eukaryotic proteins. Substrate entry into the 20S first requires opening of gating loops through binding of HbYX motifs that are present at the C-termini of certain proteasome activators (PAs). The HbYX motif has been predominantly characterized in the archaeal 20S, whereas little is known about the sequence preferences of the human 20S (h20S). Here, we synthesize and screen ~120 HbYX-like peptides, revealing unexpected differences from the archaeal system and defining the h20S recognition sequence as the Y-F/Y (YФ) motif. To gain further insight, we create a functional chimera of the optimized sequence, NLSYYT, fused to the model activator, PA26. A cryo-EM structure of PA26-h20S is used to identify key interactions, including non-canonical contacts and gate-opening mechanisms. Finally, we demonstrate that the YФ sequence preferences are tuned by valency, allowing multivalent PAs to sample greater sequence space. These results expand the model for termini-mediated gating and provide a template for the design of h20S activators. 履歴 登録 2020年6月30日 - ヘッダ(付随情報) 公開 2020年7月22日 - マップ公開 2020年7月22日 - 更新 2024年5月15日 - 現状 2024年5月15日 処理サイト : RCSB / 状態 : 公開
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