9QBF
HER2/ErbB2 extracellular domain (ECD) in compact conformation in complex with trastuzumab (TZB) antibody
Summary for 9QBF
| Entry DOI | 10.2210/pdb9qbf/pdb |
| EMDB information | 52997 |
| Descriptor | Receptor tyrosine-protein kinase erbB-2,Green fluorescent protein (1 entity in total) |
| Functional Keywords | receptor, tyrosine kinase, transmembrane, her2, signaling protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 1 |
| Total formula weight | 146737.17 |
| Authors | |
| Primary citation | 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 Cited by 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: 40712014DOI: 10.1126/sciadv.adu9945 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.8 Å) |
Structure validation
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