登録情報 データベース : EMDB / ID : EMD-14085 構造の表示 ダウンロードとリンクタイトル 26S proteasome Rpt1-RK -Ubp6-UbVS complex in the s2 state マップデータ 詳細 試料複合体 : 26S proteasome Rpt1-RK -Ubp6-UbVS complex in the s2 stateリガンド : x 3種 詳細機能・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
SAGA complex localization to transcription regulatory region / transcription export complex 2 / proteasome regulatory particle assembly / maintenance of DNA trinucleotide repeats / filamentous growth / proteasome regulatory particle, lid subcomplex / proteasome-activating activity / proteasome regulatory particle, base subcomplex / proteasome core complex / Cross-presentation of soluble exogenous antigens (endosomes) ... SAGA complex localization to transcription regulatory region / transcription export complex 2 / proteasome regulatory particle assembly / maintenance of DNA trinucleotide repeats / filamentous growth / proteasome regulatory particle, lid subcomplex / proteasome-activating activity / proteasome regulatory particle, base subcomplex / proteasome core complex / Cross-presentation of soluble exogenous antigens (endosomes) / TNFR2 non-canonical NF-kB pathway / proteasomal ubiquitin-independent protein catabolic process / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Regulation of PTEN stability and activity / KEAP1-NFE2L2 pathway / CDK-mediated phosphorylation and removal of Cdc6 / Neddylation / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / regulation of protein catabolic process / Orc1 removal from chromatin / protein deubiquitination / MAPK6/MAPK4 signaling / proteasome storage granule / Antigen processing: Ubiquitination & Proteasome degradation / proteasome assembly / proteasome endopeptidase complex / proteasome core complex, beta-subunit complex / proteasome core complex, alpha-subunit complex / threonine-type endopeptidase activity / Ub-specific processing proteases / mRNA export from nucleus / enzyme regulator activity / protein folding chaperone / Neutrophil degranulation / proteasome complex / double-strand break repair via homologous recombination / metallopeptidase activity / protein-macromolecule adaptor activity / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / endopeptidase activity / ubiquitinyl hydrolase 1 / cysteine-type deubiquitinase activity / molecular adaptor activity / regulation of cell cycle / ubiquitin protein ligase binding / structural molecule activity / endoplasmic reticulum / ATP hydrolysis activity / positive regulation of transcription by RNA polymerase II / ATP binding / nucleus / cytoplasm / cytosol 類似検索 - 分子機能 26S proteasome non-ATPase regulatory subunit 3 / 26S Proteasome non-ATPase regulatory subunit 6 / 26S Proteasome non-ATPase regulatory subunit 12 / Proteasome subunit Rpn10 / 26S Proteasome regulatory subunit 7 / 26S Proteasome regulatory subunit 6A / 26S Proteasome non-ATPase regulatory subunit 14 / 26S proteasome regulatory subunit 8 / 26S Proteasome regulatory subunit 6B / 26S proteasome regulatory subunit P45-like ... 26S proteasome non-ATPase regulatory subunit 3 / 26S Proteasome non-ATPase regulatory subunit 6 / 26S Proteasome non-ATPase regulatory subunit 12 / Proteasome subunit Rpn10 / 26S Proteasome regulatory subunit 7 / 26S Proteasome regulatory subunit 6A / 26S Proteasome non-ATPase regulatory subunit 14 / 26S proteasome regulatory subunit 8 / 26S Proteasome regulatory subunit 6B / 26S proteasome regulatory subunit P45-like / Ubiquitin carboxyl-terminal hydrolase 14-like / Rpn9, C-terminal helix / Rpn9 C-terminal helix / Proteasomal ubiquitin receptor Rpn13/ADRM1 / Proteasomal ubiquitin receptor Rpn13/ADRM1, Pru domain superfamily / Rpn13/ADRM1, Pru domain / Proteasome complex subunit Rpn13, Pru domain / Pru (pleckstrin-like receptor for ubiquitin) domain profile. / : / 26S proteasome non-ATPase regulatory subunit Rpn12 / 26S proteasome regulatory subunit, C-terminal / Proteasome regulatory subunit C-terminal / DSS1/SEM1 / 26S proteasome regulatory subunit RPN5, C-terminal domain / : / DSS1/SEM1 family / 26S proteasome regulatory subunit RPN5 C-terminal domain / 26S proteasome subunit RPN2, N-terminal domain / DSS1_SEM1 / 26S proteasome regulatory subunit Rpn6, N-terminal / 6S proteasome subunit Rpn6, C-terminal helix domain / 26S proteasome regulatory subunit RPN6 N-terminal domain / 26S proteasome subunit RPN6 C-terminal helix domain / 26S proteasome regulatory complex, non-ATPase subcomplex, Rpn2/Psmd1 subunit / 26S Proteasome non-ATPase regulatory subunit 13 / 26S proteasome regulatory subunit RPN2, C-terminal / 26S proteasome regulatory subunit RPN2 C-terminal domain / 26S Proteasome non-ATPase regulatory subunit 7/8 / 26S proteasome regulatory complex, non-ATPase subcomplex, Rpn1 subunit / RPN1, N-terminal / 26S proteasome non-ATPase regulatory subunit RPN1, C-terminal / RPN1 N-terminal domain / 26S proteasome non-ATPase regulatory subunit RPN1 C-terminal / 26S proteasome regulatory subunit Rpn7, N-terminal / 26S proteasome regulatory subunit Rpn7/COP9 signalosome complex subunit 1 / 26S proteasome subunit RPN7 / 26S Proteasome non-ATPase regulatory subunit 12/COP9 signalosome complex subunit 4 / Proteasome/cyclosome repeat / Proteasome/cyclosome repeat / von Willebrand factor type A domain / CSN8/PSMD8/EIF3K / CSN8/PSMD8/EIF3K family / HEAT repeats / Rpn11/EIF3F, C-terminal / Maintenance of mitochondrial structure and function / Proteasomal ATPase OB C-terminal domain / Proteasomal ATPase OB C-terminal domain / Ubiquitin specific protease (USP) domain signature 2. / Ubiquitin specific protease (USP) domain signature 1. / Ubiquitin specific protease, conserved site / motif in proteasome subunits, Int-6, Nip-1 and TRIP-15 / PCI domain / Proteasome component (PCI) domain / PCI domain profile. / Peptidase C19, ubiquitin carboxyl-terminal hydrolase / Ubiquitin carboxyl-terminal hydrolase / Ubiquitin specific protease domain / Ubiquitin specific protease (USP) domain profile. / Ubiquitin interacting motif / Ubiquitin-interacting motif (UIM) domain profile. / JAB1/Mov34/MPN/PAD-1 ubiquitin protease / 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 alpha-type subunit / Proteasome alpha-type subunit profile. / Proteasome B-type subunit / Proteasome beta-type subunit profile. / VWFA domain profile. / Proteasome subunit / Proteasome, subunit alpha/beta / von Willebrand factor, type A / AAA ATPase, AAA+ lid domain / AAA+ lid domain / ATPase, AAA-type, conserved site / AAA-protein family signature. / JAB/MPN domain / JAB1/MPN/MOV34 metalloenzyme domain / TPR repeat profile. 類似検索 - ドメイン・相同性 PRE5 isoform 1 / RPN13 isoform 1 / RPN10 isoform 1 / RPT1 isoform 1 / 26S proteasome regulatory subunit RPN11 / RPT6 isoform 1 / PRE9 isoform 1 / PUP2 isoform 1 / Ubiquitin carboxyl-terminal hydrolase / SCL1 isoform 1 ... PRE5 isoform 1 / RPN13 isoform 1 / RPN10 isoform 1 / RPT1 isoform 1 / 26S proteasome regulatory subunit RPN11 / RPT6 isoform 1 / PRE9 isoform 1 / PUP2 isoform 1 / Ubiquitin carboxyl-terminal hydrolase / SCL1 isoform 1 / RPT3 isoform 1 / RPN5 isoform 1 / PRE7 isoform 1 / Proteasome subunit beta / PRE6 isoform 1 / RPN7 isoform 1 / RPT2 isoform 1 / proteasome endopeptidase complex / PRE10 isoform 1 / proteasome endopeptidase complex / RPT5 isoform 1 / RPT4 isoform 1 / PUP3 isoform 1 / RPN6 isoform 1 / RPN3 isoform 1 / PRE8 isoform 1 / RPN12 isoform 1 / Ubiquitin B / 26S proteasome complex subunit SEM1 / Proteasome subunit beta type-7 / 26S proteasome regulatory subunit RPN2 / Proteasome subunit beta type-1 / 26S proteasome regulatory subunit RPN1 / 26S proteasome regulatory subunit RPN9 / 26S proteasome regulatory subunit RPN8 類似検索 - 構成要素生物種 Saccharomyces cerevisiae (パン酵母) / baker's yeast (パン酵母) / Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 6.3 Å 詳細 データ登録者Hung KYS / Klumpe S / Eisele MR / Elsasser S / Geng TT / Cheng TC / Joshi T / Rudack T / Sakata E / Finley D 資金援助 ドイツ, 5件 詳細 詳細を隠すOrganization Grant number 国 German Research Foundation (DFG) EXC 2067/1- 390729940 ドイツ German Research Foundation (DFG) SFB1035/Project A01 ドイツ German Research Foundation (DFG) CRC889/Project A11 ドイツ Other government Marie Curie Career Integration grant (PCIG14-GA-2013-631577) Other government National Institutes of Health R01 GM043601
引用ジャーナル : Nat Commun / 年 : 2022タイトル : Allosteric control of Ubp6 and the proteasome via a bidirectional switch.著者: Ka Ying Sharon Hung / Sven Klumpe / Markus R Eisele / Suzanne Elsasser / Geng Tian / Shuangwu Sun / Jamie A Moroco / Tat Cheung Cheng / Tapan Joshi / Timo Seibel / Duco Van Dalen / Xin-Hua ... 著者 : Ka Ying Sharon Hung / Sven Klumpe / Markus R Eisele / Suzanne Elsasser / Geng Tian / Shuangwu Sun / Jamie A Moroco / Tat Cheung Cheng / Tapan Joshi / Timo Seibel / Duco Van Dalen / Xin-Hua Feng / Ying Lu / Huib Ovaa / John R Engen / Byung-Hoon Lee / Till Rudack / Eri Sakata / Daniel Finley / 要旨 : The proteasome recognizes ubiquitinated proteins and can also edit ubiquitin marks, allowing substrates to be rejected based on ubiquitin chain topology. In yeast, editing is mediated by ... The proteasome recognizes ubiquitinated proteins and can also edit ubiquitin marks, allowing substrates to be rejected based on ubiquitin chain topology. In yeast, editing is mediated by deubiquitinating enzyme Ubp6. The proteasome activates Ubp6, whereas Ubp6 inhibits the proteasome through deubiquitination and a noncatalytic effect. Here, we report cryo-EM structures of the proteasome bound to Ubp6, based on which we identify mutants in Ubp6 and proteasome subunit Rpt1 that abrogate Ubp6 activation. The Ubp6 mutations define a conserved region that we term the ILR element. The ILR is found within the BL1 loop, which obstructs the catalytic groove in free Ubp6. Rpt1-ILR interaction opens the groove by rearranging not only BL1 but also a previously undescribed network of three interconnected active-site-blocking loops. Ubp6 activation and noncatalytic proteasome inhibition are linked in that they are eliminated by the same mutations. Ubp6 and ubiquitin together drive proteasomes into a unique conformation associated with proteasome inhibition. Thus, a multicomponent allosteric switch exerts simultaneous control over both Ubp6 and the proteasome. 履歴 登録 2021年12月23日 - ヘッダ(付随情報) 公開 2022年3月16日 - マップ公開 2022年3月16日 - 更新 2022年7月20日 - 現状 2022年7月20日 処理サイト : PDBe / 状態 : 公開
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