7TE8

CA14-CBD-DB21 ternary complex

7TE8 の概要

• エントリーDOI: 10.2210/pdb7te8/pdb
• 分子名称: CA14, DB21, cannabidiol, ... (4 entities in total)
• 機能のキーワード: nanobody, cannabidiol, sensor, molecular glue, biosynthetic protein
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 53548.94

構造登録者

Cao, S.,Zheng, N. (登録日: 2022-01-04, 公開日: 2022-01-12, 最終更新日: 2024-11-13)

主引用文献

Cao, S.,Kang, S.,Mao, H.,Yao, J.,Gu, L.,Zheng, N.
Defining molecular glues with a dual-nanobody cannabidiol sensor.
Nat Commun, 13:815-815, 2022

PubMed Abstract: "Molecular glue" (MG) is a term coined to describe the mechanism of action of the plant hormone auxin and subsequently used to characterize synthetic small molecule protein degraders exemplified by immune-modulatory imide drugs (IMiDs). Prospective development of MGs, however, has been hampered by its elusive definition and thermodynamic characteristics. Here, we report the crystal structure of a dual-nanobody cannabidiol-sensing system, in which the ligand promotes protein-protein interaction in a manner analogous to auxin. Through quantitative analyses, we draw close parallels among the dual-nanobody cannabidiol sensor, the auxin perception complex, and the IMiDs-bound CRL4 E3, which can bind and ubiquitinate "neo-substrates". All three systems, including the recruitment of IKZF1 and CK1α to CRBN, are characterized by the lack of ligand binding activity in at least one protein partner and an under-appreciated preexisting low micromolar affinity between the two proteinaceous subunits that is enhanced by the ligand to reach the nanomolar range. These two unifying features define MGs as a special class of proximity inducers distinct from bifunctional compounds and can be used as criteria to guide target selection for future rational discovery of MGs.

PubMed: 35145136
DOI: 10.1038/s41467-022-28507-1

実験手法

X-RAY DIFFRACTION (1.998 Å)