9LP2

Crystal structure of de novo designed amantadine induced heterodimer dAID23.4

9LP2 の概要

• エントリーDOI: 10.2210/pdb9lp2/pdb
• 分子名称: dAID23.4L, dAID23.4S, (3S,5S,7S)-tricyclo[3.3.1.1~3,7~]decan-1-amine (3 entities in total)
• 機能のキーワード: drug induced heterodimer, de novo protein
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 101396.38

構造登録者

Qihan, J.,Longxing, C. (登録日: 2025-01-23, 公開日: 2025-12-17, 最終更新日: 2026-01-14)

主引用文献

Jin, Q.,Wang, Y.,Chen, D.,Liao, J.,Cui, Z.,Fan, Y.,Zeng, A.,Xie, M.,Cao, L.
De novo design of small molecule-regulated protein oligomers.
Science, 391:-, 2026

PubMed Abstract: Small molecule-regulated protein oligomerization provides a powerful mechanism for manipulating biological processes by controlling protein proximity with high temporal precision. However, such systems only rarely exist in nature and remain a substantial challenge for de novo design. In this work, we describe a computational method for designing protein homooligomers whose assembly is regulated by small-molecule ligands with matching symmetry. We designed protein homotrimers regulated by the Food and Drug Administration (FDA)-approved drug amantadine and further designed amantadine-responsive heterodimers and heterotrimers. Biophysical characterization confirmed their amantadine-dependent assembly, and their crystal structures closely matched the design models. We demonstrated their broad applicability in controlling protein localization, membraneless condensate formation, and gene expression. Our approach opens new avenues for designing small molecule-responsive proteins and expands the chemogenetic toolkit for manipulating complex biological processes.

PubMed: 41477902
DOI: 10.1126/science.ady6017

実験手法

X-RAY DIFFRACTION (2.7 Å)