1N8Z
Crystal structure of extracellular domain of human HER2 complexed with Herceptin Fab
Summary for 1N8Z
| Entry DOI | 10.2210/pdb1n8z/pdb |
| Related | 1M6B 1N8Y |
| Descriptor | Herceptin Fab (antibody) - light chain, Herceptin Fab (antibody) - heavy chain, Receptor protein-tyrosine kinase erbB-2, ... (6 entities in total) |
| Functional Keywords | tyrosin kinase receptor, cell surface receptor, transferase |
| Biological source | Mus musculus, Homo sapiens (mouse/human) More |
| Total number of polymer chains | 3 |
| Total formula weight | 114418.80 |
| Authors | Cho, H.-S.,Mason, K.,Ramyar, K.X.,Stanley, A.M.,Gabelli, S.B.,Denney Jr., D.W.,Leahy, D.J. (deposition date: 2002-11-21, release date: 2003-02-18, Last modification date: 2024-10-30) |
| Primary citation | Cho, H.-S.,Mason, K.,Ramyar, K.X.,Stanley, A.M.,Gabelli, S.B.,Denney Jr., D.W.,Leahy, D.J. Structure of the Extracellular Region of HER2 Alone and in Complex with the Herceptin Fab Nature, 421:756-760, 2003 Cited by PubMed Abstract: HER2 (also known as Neu, ErbB2) is a member of the epidermal growth factor receptor (EGFR; also known as ErbB) family of receptor tyrosine kinases, which in humans includes HER1 (EGFR, ERBB1), HER2, HER3 (ERBB3) and HER4 (ERBB4). ErbB receptors are essential mediators of cell proliferation and differentiation in the developing embryo and in adult tissues, and their inappropriate activation is associated with the development and severity of many cancers. Overexpression of HER2 is found in 20-30% of human breast cancers, and correlates with more aggressive tumours and a poorer prognosis. Anticancer therapies targeting ErbB receptors have shown promise, and a monoclonal antibody against HER2, Herceptin (also known as trastuzumab), is currently in use as a treatment for breast cancer. Here we report crystal structures of the entire extracellular regions of rat HER2 at 2.4 A and human HER2 complexed with the Herceptin antigen-binding fragment (Fab) at 2.5 A. These structures reveal a fixed conformation for HER2 that resembles a ligand-activated state, and show HER2 poised to interact with other ErbB receptors in the absence of direct ligand binding. Herceptin binds to the juxtamembrane region of HER2, identifying this site as a target for anticancer therapies. PubMed: 12610629DOI: 10.1038/nature01392 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.52 Å) |
Structure validation
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