6M4U

Crystal structure of FKBP-FRB T2098L mutant in complex with rapamycin

6M4U の概要

• エントリーDOI: 10.2210/pdb6m4u/pdb
• 分子名称: Peptidyl-prolyl cis-trans isomerase FKBP1A, Serine/threonine-protein kinase mTOR, RAPAMYCIN IMMUNOSUPPRESSANT DRUG, ... (7 entities in total)
• 機能のキーワード: rapamycin, complex, kinase, isomerase
• 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: 50202.19

構造登録者

Kikuchi, M.,Wu, D.,Inoue, T.,Umehara, T. (登録日: 2020-03-09, 公開日: 2020-08-26, 最終更新日: 2023-11-29)

主引用文献

Wu, H.D.,Kikuchi, M.,Dagliyan, O.,Aragaki, A.K.,Nakamura, H.,Dokholyan, N.V.,Umehara, T.,Inoue, T.
Rational design and implementation of a chemically inducible heterotrimerization system.
Nat.Methods, 17:928-936, 2020

PubMed Abstract: Chemically inducible dimerization (CID) uses a small molecule to induce binding of two different proteins. CID tools such as the FK506-binding protein-FKBP-rapamycin-binding- (FKBP-FRB)-rapamycin system have been widely used to probe molecular events inside and outside cells. While various CID tools are available, chemically inducible trimerization (CIT) does not exist, due to inherent challenges in designing a chemical that simultaneously binds three proteins with high affinity and specificity. Here, we developed CIT by rationally splitting FRB and FKBP. Cellular and structural datasets showed efficient trimerization of split pairs of FRB or FKBP with full-length FKBP or FRB, respectively, by rapamycin. CIT rapidly induced tri-organellar junctions and perturbed intended membrane lipids exclusively at select membrane contact sites. By conferring one additional condition to what is achievable with CID, CIT expands the types of manipulation in single live cells to address cell biology questions otherwise intractable and engineer cell functions for future synthetic biology applications.

PubMed: 32747768
DOI: 10.1038/s41592-020-0913-x

実験手法

X-RAY DIFFRACTION (2.2 Å)