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基本情報
登録情報 | データベース: PDB / ID: 8s7d | |||||||||||||||||||||
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タイトル | Cryo-EM structure of SKP1-FBXO22 in complex with a BACH1 BTB dimer at 3.2A resolution | |||||||||||||||||||||
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![]() | LIGASE / SKP1-FBXO22 E3 ligase SCF F-box protein BACH1 BTB | |||||||||||||||||||||
機能・相同性 | ![]() regulation of skeletal muscle fiber development / Regulation of HMOX1 expression and activity / F-box domain binding / PcG protein complex / ligand-modulated transcription factor activity / positive regulation of ubiquitin protein ligase activity / Cul7-RING ubiquitin ligase complex / maintenance of protein location in nucleus / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / nucleocytoplasmic transport ...regulation of skeletal muscle fiber development / Regulation of HMOX1 expression and activity / F-box domain binding / PcG protein complex / ligand-modulated transcription factor activity / positive regulation of ubiquitin protein ligase activity / Cul7-RING ubiquitin ligase complex / maintenance of protein location in nucleus / Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling / nucleocytoplasmic transport / regulation of metabolic process / SCF ubiquitin ligase complex / NFE2L2 regulating anti-oxidant/detoxification enzymes / SCF-dependent proteasomal ubiquitin-dependent protein catabolic process / ubiquitin ligase complex scaffold activity / Prolactin receptor signaling / cullin family protein binding / protein monoubiquitination / ubiquitin-like ligase-substrate adaptor activity / protein K48-linked ubiquitination / Nuclear events stimulated by ALK signaling in cancer / Regulation of BACH1 activity / MAP3K8 (TPL2)-dependent MAPK1/3 activation / NIK-->noncanonical NF-kB signaling / SCF-beta-TrCP mediated degradation of Emi1 / Vpu mediated degradation of CD4 / molecular function activator activity / Dectin-1 mediated noncanonical NF-kB signaling / cellular response to starvation / Activation of NF-kappaB in B cells / Iron uptake and transport / Degradation of GLI1 by the proteasome / GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2 / Negative regulation of NOTCH4 signaling / 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 / Degradation of beta-catenin by the destruction complex / NOTCH1 Intracellular Domain Regulates Transcription / Heme signaling / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / CLEC7A (Dectin-1) signaling / SCF(Skp2)-mediated degradation of p27/p21 / FCERI mediated NF-kB activation / protein modification process / beta-catenin binding / Interleukin-1 signaling / Orc1 removal from chromatin / DNA-binding transcription repressor activity, RNA polymerase II-specific / Cyclin D associated events in G1 / RNA polymerase II transcription regulator complex / Regulation of RUNX2 expression and activity / Z disc / : / protein polyubiquitination / Regulation of PLK1 Activity at G2/M Transition / ubiquitin-protein transferase activity / Downstream TCR signaling / Antigen processing: Ubiquitination & Proteasome degradation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / Neddylation / DNA-binding transcription activator activity, RNA polymerase II-specific / ubiquitin-dependent protein catabolic process / proteasome-mediated ubiquitin-dependent protein catabolic process / DNA-binding transcription factor activity, RNA polymerase II-specific / protein ubiquitination / chromatin remodeling / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / protein domain specific binding / DNA repair / heme binding / centrosome / regulation of transcription by RNA polymerase II / regulation of DNA-templated transcription / chromatin / negative regulation of transcription by RNA polymerase II / nucleoplasm / nucleus / cytosol / cytoplasm 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: 3.2 Å | |||||||||||||||||||||
![]() | Khoshouei, M. / Goretzki, B. | |||||||||||||||||||||
資金援助 | 1件
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![]() | ![]() タイトル: Dual BACH1 regulation by complementary SCF-type E3 ligases. 著者: Benedikt Goretzki / Maryam Khoshouei / Martin Schröder / Patrick Penner / Luca Egger / Christine Stephan / Dayana Argoti / Nele Dierlamm / Jimena Maria Rada / Sandra Kapps / Catrin Swantje ...著者: Benedikt Goretzki / Maryam Khoshouei / Martin Schröder / Patrick Penner / Luca Egger / Christine Stephan / Dayana Argoti / Nele Dierlamm / Jimena Maria Rada / Sandra Kapps / Catrin Swantje Müller / Zacharias Thiel / Merve Mutlu / Claude Tschopp / David Furkert / Felix Freuler / Simon Haenni / Laurent Tenaillon / Britta Knapp / Alexandra Hinniger / Philipp Hoppe / Enrico Schmidt / Sascha Gutmann / Mario Iurlaro / Grigory Ryzhakov / César Fernández / ![]() ![]() 要旨: Broad-complex, tramtrack, and bric-à-brac domain (BTB) and CNC homolog 1 (BACH1) is a key regulator of the cellular oxidative stress response and an oncogene that undergoes tight post-translational ...Broad-complex, tramtrack, and bric-à-brac domain (BTB) and CNC homolog 1 (BACH1) is a key regulator of the cellular oxidative stress response and an oncogene that undergoes tight post-translational control by two distinct F-box ubiquitin ligases, SCF and SCF. However, how both ligases recognize BACH1 under oxidative stress is unclear. In our study, we elucidate the mechanism by which FBXO22 recognizes a quaternary degron in a domain-swapped β-sheet of the BACH1 BTB dimer. Cancer-associated mutations and cysteine modifications destabilize the degron and impair FBXO22 binding but simultaneously expose an otherwise shielded degron in the dimer interface, allowing FBXL17 to recognize BACH1 as a monomer. These findings shed light on a ligase switch mechanism that enables post-translational regulation of BACH1 by complementary ligases depending on the stability of its BTB domain. Our results provide mechanistic insights into the oxidative stress response and may spur therapeutic approaches for targeting oxidative stress-related disorders and cancer. | |||||||||||||||||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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-検証レポート
文書・要旨 | ![]() | 1 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1 MB | 表示 | |
XML形式データ | ![]() | 30.3 KB | 表示 | |
CIF形式データ | ![]() | 43.3 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 19766MC ![]() 8s7eC ![]() 9gp5C ![]() 9gr9C ![]() 9graC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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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
#1: タンパク質 | 分子量: 14186.162 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #2: タンパク質 | | 分子量: 18679.965 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P63208 #3: タンパク質 | | 分子量: 43597.062 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q8NEZ5 Has protein modification | N | |
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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 |
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分子量 | 値: 62 kDa/nm / 実験値: YES | ||||||||||||||||||||||||
由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 7.5 | ||||||||||||||||||||||||
試料 | 濃度: 20 mg/ml / 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 / 最大 デフォーカス(公称値): 1600 nm / 最小 デフォーカス(公称値): 600 nm |
撮影 | 電子線照射量: 50 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) 詳細: THERMO SCIENTIFIC FALCON 4i (4k x 4k) direct detector |
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解析
EMソフトウェア | 名称: PHENIX / カテゴリ: モデル精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 1715031 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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