8HGS

The EGF-bound EGFR ectodomain homodimer

8HGS の概要

• エントリーDOI: 10.2210/pdb8hgs/pdb
• EMDBエントリー: 34746
• 分子名称: Epidermal growth factor receptor, Pro-epidermal growth factor, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-3)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 177643.54

構造登録者

Zhang, Z.,Bai, X. (登録日: 2022-11-15, 公開日: 2023-02-15, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.81 Å)