9QBF

HER2/ErbB2 extracellular domain (ECD) in compact conformation in complex with trastuzumab (TZB) antibody

9QBF の概要

• エントリーDOI: 10.2210/pdb9qbf/pdb
• EMDBエントリー: 52997
• 分子名称: Receptor tyrosine-protein kinase erbB-2,Green fluorescent protein (1 entity in total)
• 機能のキーワード: receptor, tyrosine kinase, transmembrane, her2, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 146737.17

構造登録者

Gragera, M.,Buschiazzo, A.,Vacca, S. (登録日: 2025-03-02, 公開日: 2025-08-06)

主引用文献

Vacca, S.,Gragera, M.,Buschiazzo, A.,Herreros, D.,Krieger, J.M.,Bonn-Garcia, S.,Melero, R.,Sorzano, C.O.,Carazo, J.M.,Medalia, O.,Pluckthun, A.
Structural analysis of HER2-trastuzumab complex reveals receptor conformational adaptation.
Sci Adv, 11:eadu9945-eadu9945, 2025

PubMed Abstract: 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.

PubMed: 40712014
DOI: 10.1126/sciadv.adu9945

実験手法

ELECTRON MICROSCOPY (3.8 Å)