Human epidermal growth factor receptor 2 extracellular domain IV (HER2 ECD IV)

Domain IV of the human epidermal growth factor receptor 2 (HER2/ERBB2) is part of the extracellular region that contributes to receptor dimerization and signal transduction in cells. HER2 comprises four extracellular domains (I-IV), with domain IV forming a critical component of the dimerization and activation process, albeit with a less understood mechanistic role compared to other domains[1][4]. Domain IV consists predominantly of β-strand/β-turn and loop structures held by disulfide bonds, and lacks significant α-helical content[3]. This subdomain is the principal binding site for the antibody trastuzumab, which interferes with HER2 dimerization and blocks oncogenic signaling, making it a prime therapeutic target in cancers that overexpress HER2, notably breast and gastric cancers[3][5][7]. Drugs targeting domain IV disrupt HER2-driven proliferation and exert antitumor effects, but also carry safety risks such as cardiotoxicity and therapy resistance. HER2-overexpression and serum HER2 ECD levels function as biomarkers for cancer prognosis and response to targeted therapy[3][7].

Other names

HER2 domain IVHER2/ERBB2 domain IVERBB2 domain IVHER2 D-IVHER2 subdomain IV

Inhibition of HER2 dimerization and downstream signaling; Blockade of ligand-independent activation; Antibody-dependent cellular cytotoxicity (ADCC)