Human epidermal growth factor receptors (HERs or ErbBs) play crucial roles in numerous cellular processes. ErbB2 is a key member of ErbB family, and its overexpression is recognized as a frequent molecular abnormality. In cancer, this overexpression correlates with aggressive disease and poor patient outcomes. Dimer-dependent phosphorylation is a key event for the signal transduction of ErbBs. However, the molecular mechanism of the dimerization of ErbB2 remains elusive. In the present work, we report the homodimer architecture of the ErbB2 extracellular domain (ECD) which is unique compared with other dimer-models of ErbBs. The structure of the ErbB2 ECD homodimer represents a "back to head" interaction, in which a protruding β-hairpin arm in domain II of one ErbB2 protomer is inserted into a C-shaped pocket created by domains I-III of the adjacent ErbB2 protomer. This dimerized architecture and its impact on the phosphorylation of ErbB2 intracellular domain were further verified by a mutagenesis study. We also elucidated the different impacts of two clinically administered therapeutic antibodies, trastuzumab and pertuzumab, on ErbB2 dimerization. This information not only provides an understanding of the molecular mechanism of ErbBs dimerization but also elucidates ErbB2-targeted therapy at the molecular level. In our experiment, we use both of antibody H chain and antibody L chain, which are from 3WLW(Molecular Architecture Of The Erbb2 Extracellular Domain Homodimer). And we use the (GGGGS)3 linker to connect them.
Sequence and Features
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- 21Illegal BglII site found at 24
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HER2 is a membrane tyrosine kinase and an oncogene. Studies have shown it to be overexpressed and gene amplified in about 20% of the breast cancers. On activation it provides the cell with potent proliferative and anti-apoptosis signals. It is one of the major driver of tumor development and progression for a subset of breast cancer. This part contains Anti-HER2 single chain variable fragment.
1. Gutierrez, C., & Schiff, R. (2011). HER2: biology, detection, and clinical implications. Archives of pathology & laboratory medicine, 135(1), 55–62. https://doi.org/10.1043/2010-0454-RAR.1