+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8hgp | ||||||
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タイトル | The EREG-bound EGFR/HER2 ectodomain complex | ||||||
要素 |
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キーワード | MEMBRANE PROTEIN (膜タンパク質) | ||||||
機能・相同性 | 機能・相同性情報 luteinizing hormone signaling pathway / ovarian cumulus expansion / 排卵 / ERBB4-ERBB4 signaling pathway / negative regulation of smooth muscle cell differentiation / negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus ...luteinizing hormone signaling pathway / ovarian cumulus expansion / 排卵 / ERBB4-ERBB4 signaling pathway / negative regulation of smooth muscle cell differentiation / negative regulation of immature T cell proliferation in thymus / ERBB3:ERBB2 complex / ERBB2-ERBB4 signaling pathway / GRB7 events in ERBB2 signaling / immature T cell proliferation in thymus / RNA polymerase I core binding / primary follicle stage / female meiotic nuclear division / PI3K events in ERBB4 signaling / regulation of microtubule-based process / ErbB-3 class receptor binding / positive regulation of innate immune response / semaphorin receptor complex / Sema4D induced cell migration and growth-cone collapse / motor neuron axon guidance / response to hydroxyisoflavone / multivesicular body, internal vesicle lumen / positive regulation of prolactin secretion / negative regulation of cardiocyte differentiation / neurotransmitter receptor localization to postsynaptic specialization membrane / positive regulation of protein kinase C activity / 転写 (生物学) / oocyte maturation / diterpenoid metabolic process / Shc-EGFR complex / 月経周期 / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity / EGFR interacts with phospholipase C-gamma / positive regulation of mucus secretion / response to UV-A / epidermal growth factor binding / PLCG1 events in ERBB2 signaling / tongue development / midgut development / ERBB2-EGFR signaling pathway / hydrogen peroxide metabolic process / PTK6 promotes HIF1A stabilization / digestive tract morphogenesis / regulation of nitric-oxide synthase activity / epidermal growth factor receptor binding / neuromuscular junction development / positive regulation of Rho protein signal transduction / morphogenesis of an epithelial fold / ERBB2 Activates PTK6 Signaling / intracellular vesicle / Drug-mediated inhibition of ERBB2 signaling / Resistance of ERBB2 KD mutants to trastuzumab / Resistance of ERBB2 KD mutants to sapitinib / Resistance of ERBB2 KD mutants to tesevatinib / Resistance of ERBB2 KD mutants to neratinib / Resistance of ERBB2 KD mutants to osimertinib / Resistance of ERBB2 KD mutants to afatinib / Resistance of ERBB2 KD mutants to AEE788 / Resistance of ERBB2 KD mutants to lapatinib / Drug resistance in ERBB2 TMD/JMD mutants / enzyme-linked receptor protein signaling pathway / positive regulation of transcription by RNA polymerase I / Signaling by EGFR / response to cobalamin / ERBB2-ERBB3 signaling pathway / transmembrane receptor protein tyrosine kinase activator activity / protein tyrosine kinase activator activity / negative regulation of epidermal growth factor receptor signaling pathway / Signaling by ERBB4 / regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / eyelid development in camera-type eye / oligodendrocyte differentiation / protein insertion into membrane / cerebral cortex cell migration / ERBB2 Regulates Cell Motility / semaphorin-plexin signaling pathway / regulation of JNK cascade / positive regulation of cell division / : / PI3K events in ERBB2 signaling / positive regulation of cyclin-dependent protein serine/threonine kinase activity / keratinocyte proliferation / positive regulation of cell adhesion / negative regulation of mitotic cell cycle / hair follicle development / SHC1 events in ERBB4 signaling / MAP kinase kinase kinase activity / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / positive regulation of protein targeting to membrane / anatomical structure morphogenesis / embryonic placenta development / positive regulation of protein kinase activity / positive regulation of bone resorption / positive regulation of G1/S transition of mitotic cell cycle / GAB1 signalosome / positive regulation of nitric oxide mediated signal transduction / regulation of angiogenesis / coreceptor activity / Schwann cell development 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: 4.53 Å | ||||||
データ登録者 | Zhang, Z. / Bai, X. | ||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Cell Discov / 年: 2023 タイトル: Structure and dynamics of the EGFR/HER2 heterodimer. 著者: Xue Bai / Pengyu Sun / Xinghao Wang / Changkun Long / Shuyun Liao / Song Dang / Shangshang Zhuang / Yongtao Du / Xinyi Zhang / Nan Li / Kangmin He / Zhe Zhang / 要旨: HER2 belongs to the human epidermal growth factor receptor tyrosine kinase family. Its overexpression or hyperactivation is a leading cause for multiple types of cancers. HER2 functions mainly ...HER2 belongs to the human epidermal growth factor receptor tyrosine kinase family. Its overexpression or hyperactivation is a leading cause for multiple types of cancers. HER2 functions mainly through dimerization with other family members, such as EGFR. However, the molecular details for heterodimer assembly have not been completely understood. Here, we report cryo-EM structures of the EGF- and epiregulin-bound EGFR/HER2 ectodomain complexes at resolutions of 3.3 Å and 4.5 Å, respectively. Together with the functional analyses, we demonstrate that only the dimerization arm of HER2, but not that of EGFR, is essential for their heterodimer formation and signal transduction. Moreover, we analyze the differential membrane dynamics and transient interactions of endogenous EGFR and HER2 molecules in genome-edited cells using single-molecule live-cell imaging. Furthermore, we show that the interaction with HER2 could allow EGFR to resist endocytosis. Together, this work deepens our understanding of the unique structural properties and dynamics of the EGFR/HER2 complex. | ||||||
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 | 8hgp.cif.gz | 221.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8hgp.ent.gz | 175.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8hgp.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/hg/8hgp ftp://data.pdbj.org/pub/pdb/validation_reports/hg/8hgp | HTTPS FTP |
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-関連構造データ
関連構造データ | 34745MC 8hgoC 8hgsC 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
-タンパク質 , 2種, 2分子 BA
#1: タンパク質 | 分子量: 82149.758 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: ERBB2, HER2, MLN19, NEU, NGL / 細胞株 (発現宿主): HEK293S GnTI- / 発現宿主: Homo sapiens (ヒト) 参照: UniProt: P04626, 受容体型チロシンキナーゼ |
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#2: タンパク質 | 分子量: 81075.297 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: EGFR, ERBB, ERBB1, HER1 / 細胞株 (発現宿主): HEK293S GnTI- / 発現宿主: Homo sapiens (ヒト) 参照: UniProt: P00533, 受容体型チロシンキナーゼ |
-タンパク質・ペプチド , 1種, 1分子 C
#3: タンパク質・ペプチド | 分子量: 5578.410 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: EREG / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: O14944 |
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-糖 , 3種, 4分子
#4: 多糖 | alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose タイプ: oligosaccharideオリゴ糖 / 分子量: 748.682 Da / 分子数: 1 / 由来タイプ: 組換発現 |
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#5: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose |
#6: 糖 |
-詳細
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: EREG-bound EGFR/HER2 ectodomain complex / タイプ: COMPLEX / Entity ID: #1-#3 / 由来: RECOMBINANT |
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分子量 | 値: 0.2 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: Homo sapiens (ヒト) / 細胞: HEK293S GnTI- |
緩衝液 | pH: 7.5 |
試料 | 濃度: 4.2 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 / 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 FIELDBright-field microscopy / 最大 デフォーカス(公称値): 1500 nm / 最小 デフォーカス(公称値): 1200 nm |
撮影 | 電子線照射量: 60.8 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 4.53 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 273388 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
原子モデル構築 | プロトコル: FLEXIBLE FIT / 空間: REAL | ||||||||||||||||||||||||
拘束条件 |
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