8HGP

The EREG-bound EGFR/HER2 ectodomain complex

Summary for 8HGP

• Entry DOI: 10.2210/pdb8hgp/pdb
• EMDB information: 34745
• Descriptor: Receptor tyrosine-protein kinase erbB-2, Epidermal growth factor receptor, Proepiregulin, ... (6 entities in total)
• Functional Keywords: membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 170418.96

Authors

Zhang, Z.,Bai, X. (deposition date: 2022-11-15, release date: 2023-02-08, Last modification date: 2023-03-01)

Primary citation

Bai, X.,Sun, P.,Wang, X.,Long, C.,Liao, S.,Dang, S.,Zhuang, S.,Du, Y.,Zhang, X.,Li, N.,He, K.,Zhang, Z.
Structure and dynamics of the EGFR/HER2 heterodimer.
Cell Discov, 9:18-18, 2023

PubMed Abstract: HER2 belongs to the human epidermal growth factor receptor tyrosine kinase family. Its overexpression or hyperactivation is a leading cause for multiple types of cancers. HER2 functions mainly through dimerization with other family members, such as EGFR. However, the molecular details for heterodimer assembly have not been completely understood. Here, we report cryo-EM structures of the EGF- and epiregulin-bound EGFR/HER2 ectodomain complexes at resolutions of 3.3 Å and 4.5 Å, respectively. Together with the functional analyses, we demonstrate that only the dimerization arm of HER2, but not that of EGFR, is essential for their heterodimer formation and signal transduction. Moreover, we analyze the differential membrane dynamics and transient interactions of endogenous EGFR and HER2 molecules in genome-edited cells using single-molecule live-cell imaging. Furthermore, we show that the interaction with HER2 could allow EGFR to resist endocytosis. Together, this work deepens our understanding of the unique structural properties and dynamics of the EGFR/HER2 complex.

PubMed: 36781849
DOI: 10.1038/s41421-023-00523-5

Experimental method

ELECTRON MICROSCOPY (4.53 Å)