2026-09-29 九州大学
薬剤の違いによって変化するエストロゲン受容体αの動き(左)と 表紙に採択されたイメージ図(右)
＜関連情報＞
- https://www.kyushu-u.ac.jp/ja/researches/view/1580
- https://pubs.acs.org/jpclcd/article/17/37/10594/5421124/High-Speed-Atomic-Force-Microscopy-Reveals-Single
高速原子間力顕微鏡により、フルベストラント結合エストロゲン受容体αの単一分子ダイナミクスが明らかになる High-Speed Atomic Force Microscopy Reveals Single-Molecule Dynamics of Fulvestrant-Bound Estrogen Receptor α
Reon Imakawa;Kota Aramaki;Takeru Kajiyama;Kota Yoshimura;Towa Onohara;Keesiang Lim;Richard W. Wong;Ayami Matsushima
The Journal of Physical Chemistry Letters Published:September 04, 2026
DOI:https://doi.org/10.1021/acs.jpclett.6c01784
Abstract
Fulvestrant is a selective estrogen receptor downregulator (SERD) that antagonizes estrogen receptor α (ERα) and also promotes receptor degradation. However, how it affects full-length ERα dynamics at the single-molecule level remains unclear. Here, we used high-speed atomic force microscopy (HS-AFM) to directly visualize the dynamic behavior of full-length ERα under fulvestrant-bound, ligand-free, and other ligand-bound conditions. Among the four conditions, fulvestrant-bound ERα alone showed a reduced apparent molecular volume and increased surface mobility, behaving distinctly from the ligand-free, E2-bound, and 4-OHT-bound states. These results indicate that fulvestrant not only drives ERα inactivation and degradation but also is associated with changes in the observed molecular morphology and dynamics of full-length ERα. Our study provides direct single-molecule observation of altered molecular behavior under fulvestrant-bound conditions, which we interpret as reflecting changes in the conformational ensemble of full-length ERα.
