ジャーナル: Sci Adv / 年: 2025 タイトル: Structural analysis of HER2-trastuzumab complex reveals receptor conformational adaptation. 著者: Santiago Vacca / Marcos Gragera / Alejandro Buschiazzo / David Herreros / James M Krieger / Santiago Bonn-Garcia / Roberto Melero / Carlos Os Sorzano / Jose M Carazo / Ohad Medalia / Andreas Plückthun / 要旨: Human epidermal growth factor receptor-2 (HER2) is a receptor tyrosine kinase, associated with a variety of malignant tumors, usually through overexpression, resulting in aberrant signaling. ...Human epidermal growth factor receptor-2 (HER2) is a receptor tyrosine kinase, associated with a variety of malignant tumors, usually through overexpression, resulting in aberrant signaling. Trastuzumab (TZB), one of the monoclonal antibodies (mAbs) used in combination with chemotherapy, has become a major therapeutic for HER2-overexpressing cancers. Current structural understanding of HER2 and its interactions with other receptors and with different affinity agents has relied on numerous structures of individual domains of HER2. Here, we subjected purified near full-length HER2 to single-particle cryo-electron microscopy (cryo-EM) analysis. Besides the canonical conformation described in previous structural studies, we report a previously unreported conformation of the HER2 extracellular domain that is stabilized upon TZB binding, which might hamper association with HER3, a receptor with which HER2 forms an oncogenic unit. Together, our findings provide insights into the conformational dynamics of the HER2 receptor and the mechanism of action of TZB.
全体 : Ternary complex of HER2/ErbB2 in its canonical conformation with ...
全体
名称: Ternary complex of HER2/ErbB2 in its canonical conformation with trastuzumab (TZB) antibody.
要素
複合体: Ternary complex of HER2/ErbB2 in its canonical conformation with trastuzumab (TZB) antibody.
タンパク質・ペプチド: Receptor tyrosine-protein kinase erbB-2,Green fluorescent protein
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超分子 #1: Ternary complex of HER2/ErbB2 in its canonical conformation with ...
超分子
名称: Ternary complex of HER2/ErbB2 in its canonical conformation with trastuzumab (TZB) antibody. タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all 詳細: Near-full length HER2/ErbB2 in complex with full length humanized monoclonal antibody trastuzumab (TZB). The final reconstruction contains only the HER2 ECD.
由来(天然)
生物種: Homo sapiens (ヒト)
分子量
理論値: 112 KDa
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分子 #1: Receptor tyrosine-protein kinase erbB-2,Green fluorescent protein
分子
名称: Receptor tyrosine-protein kinase erbB-2,Green fluorescent protein タイプ: protein_or_peptide / ID: 1 詳細: Near-full length HER2/ErbB2 in complex with full length humanized monoclonal antibody trastuzumab (TZB). The final reconstruction contains only the HER2 ECD head (from residues S22 to E542). ...詳細: Near-full length HER2/ErbB2 in complex with full length humanized monoclonal antibody trastuzumab (TZB). The final reconstruction contains only the HER2 ECD head (from residues S22 to E542).,Near-full length HER2/ErbB2 in complex with full length humanized monoclonal antibody trastuzumab (TZB). The final reconstruction contains only the HER2 ECD head (from residues S22 to E542). コピー数: 1 / 光学異性体: LEVO / EC番号: receptor protein-tyrosine kinase