+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7yeh | ||||||
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タイトル | Cryo-EM structure of human OGT-OGA complex | ||||||
要素 |
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キーワード | TRANSFERASE/HYDROLASE / O-GlcNAc transferase / O-GlcNAcase / Complex / Mutual inhibition / TRANSFERASE / TRANSFERASE-HYDROLASE complex | ||||||
機能・相同性 | 機能・相同性情報 protein N-acetylglucosaminyltransferase complex / hyalurononglucosaminidase activity / protein O-GlcNAc transferase / glycoprotein metabolic process / regulation of insulin receptor signaling pathway / protein O-acetylglucosaminyltransferase activity / N-acetylglucosamine metabolic process / positive regulation of transcription from RNA polymerase II promoter by glucose / glycoprotein catabolic process / protein O-GlcNAcase ...protein N-acetylglucosaminyltransferase complex / hyalurononglucosaminidase activity / protein O-GlcNAc transferase / glycoprotein metabolic process / regulation of insulin receptor signaling pathway / protein O-acetylglucosaminyltransferase activity / N-acetylglucosamine metabolic process / positive regulation of transcription from RNA polymerase II promoter by glucose / glycoprotein catabolic process / protein O-GlcNAcase / : / : / [protein]-3-O-(N-acetyl-D-glucosaminyl)-L-serine/L-threonine O-N-acetyl-alpha-D-glucosaminase activity / acetylglucosaminyltransferase activity / regulation of necroptotic process / regulation of Rac protein signal transduction / negative regulation of stem cell population maintenance / protein O-linked glycosylation / protein deglycosylation / NSL complex / regulation of glycolytic process / regulation of neurotransmitter receptor localization to postsynaptic specialization membrane / RIPK1-mediated regulated necrosis / regulation of synapse assembly / regulation of gluconeogenesis / positive regulation of stem cell population maintenance / Formation of WDR5-containing histone-modifying complexes / phosphatidylinositol-3,4,5-trisphosphate binding / positive regulation of proteolysis / mitophagy / hemopoiesis / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / histone acetyltransferase complex / positive regulation of lipid biosynthetic process / negative regulation of protein ubiquitination / positive regulation of TORC1 signaling / negative regulation of cell migration / response to nutrient / cell projection / positive regulation of translation / mitochondrial membrane / beta-N-acetylglucosaminidase activity / cellular response to glucose stimulus / negative regulation of transforming growth factor beta receptor signaling pathway / circadian regulation of gene expression / response to insulin / Regulation of necroptotic cell death / protein processing / chromatin DNA binding / UCH proteinases / chromatin organization / positive regulation of cold-induced thermogenesis / HATs acetylate histones / glutamatergic synapse / apoptotic process / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / signal transduction / positive regulation of transcription by RNA polymerase II / protein-containing complex / nucleoplasm / identical protein binding / membrane / nucleus / plasma membrane / cytosol 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
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: 3.92 Å | ||||||
データ登録者 | Lu, P. / Liu, Y. / Yu, H. / Gao, H. | ||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2023 タイトル: Cryo-EM structure of human O-GlcNAcylation enzyme pair OGT-OGA complex. 著者: Ping Lu / Yusong Liu / Maozhou He / Ting Cao / Mengquan Yang / Shutao Qi / Hongtao Yu / Haishan Gao / 要旨: O-GlcNAcylation is a conserved post-translational modification that attaches N-acetyl glucosamine (GlcNAc) to myriad cellular proteins. In response to nutritional and hormonal signals, O- ...O-GlcNAcylation is a conserved post-translational modification that attaches N-acetyl glucosamine (GlcNAc) to myriad cellular proteins. In response to nutritional and hormonal signals, O-GlcNAcylation regulates diverse cellular processes by modulating the stability, structure, and function of target proteins. Dysregulation of O-GlcNAcylation has been implicated in the pathogenesis of cancer, diabetes, and neurodegeneration. A single pair of enzymes, the O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), catalyzes the addition and removal of O-GlcNAc on over 3,000 proteins in the human proteome. However, how OGT selects its native substrates and maintains the homeostatic control of O-GlcNAcylation of so many substrates against OGA is not fully understood. Here, we present the cryo-electron microscopy (cryo-EM) structures of human OGT and the OGT-OGA complex. Our studies reveal that OGT forms a functionally important scissor-shaped dimer. Within the OGT-OGA complex structure, a long flexible OGA segment occupies the extended substrate-binding groove of OGT and positions a serine for O-GlcNAcylation, thus preventing OGT from modifying other substrates. Conversely, OGT disrupts the functional dimerization of OGA and occludes its active site, resulting in the blocking of access by other substrates. This mutual inhibition between OGT and OGA may limit the futile O-GlcNAcylation cycles and help to maintain O-GlcNAc homeostasis. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7yeh.cif.gz | 453.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7yeh.ent.gz | 351.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7yeh.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 7yeh_validation.pdf.gz | 1.4 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7yeh_full_validation.pdf.gz | 1.5 MB | 表示 | |
XML形式データ | 7yeh_validation.xml.gz | 82.9 KB | 表示 | |
CIF形式データ | 7yeh_validation.cif.gz | 122.4 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ye/7yeh ftp://data.pdbj.org/pub/pdb/validation_reports/ye/7yeh | HTTPS FTP |
-関連構造データ
関連構造データ | 33773MC 7yeaC 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 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 117953.414 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: OGT 発現宿主: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (大腸菌) 参照: UniProt: O15294, protein O-GlcNAc transferase #2: タンパク質 | 分子量: 103020.906 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: OGA, HEXC, KIAA0679, MEA5, MGEA5 発現宿主: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (大腸菌) 参照: UniProt: O60502, protein O-GlcNAcase #3: 化合物 | ChemComp-UDP / | #4: 糖 | ChemComp-NAG / | 研究の焦点であるリガンドがあるか | Y | |
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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 |
-試料調製
構成要素 | 名称: Cryo-EM structure of human OGT-OGA complex / タイプ: COMPLEX / Entity ID: #1-#2 / 由来: RECOMBINANT |
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分子量 | 値: 0.4 MDa / 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (大腸菌) |
緩衝液 | pH: 7.5 |
試料 | 濃度: 5 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 |
急速凍結 | 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 277 K |
-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: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2300 nm / 最小 デフォーカス(公称値): 1300 nm / アライメント法: COMA FREE |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 電子線照射量: 50 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.18.2_3874: / 分類: 精密化 | ||||||||||||||||||||||||
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EMソフトウェア |
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 114543 | ||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.92 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 114543 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
原子モデル構築 | B value: 146 / プロトコル: RIGID BODY FIT / 空間: REAL | ||||||||||||||||||||||||
原子モデル構築 | 3D fitting-ID: 1 / PDB chain-ID: A / Source name: PDB / タイプ: experimental model
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拘束条件 |
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