5GPG

Co-crystal structure of the FK506 binding domain of human FKBP25, Rapamycin and the FRB domain of human mTOR

5GPG の概要

• エントリーDOI: 10.2210/pdb5gpg/pdb
• 分子名称: Peptidyl-prolyl cis-trans isomerase FKBP3, Serine/threonine-protein kinase mTOR, RAPAMYCIN IMMUNOSUPPRESSANT DRUG, ... (4 entities in total)
• 機能のキーワード: complex, kinase, isomerase-transferase complex, isomerase/transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• 細胞内の位置: Nucleus: Q00688; Endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side : P42345
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25314.00

構造登録者

Lee, H.B.,Lee, S.Y.,Rhee, H.W.,Lee, C.W. (登録日: 2016-08-02, 公開日: 2016-10-12, 最終更新日: 2024-11-13)

主引用文献

Lee, S.Y.,Lee, H.,Lee, H.K.,Lee, S.W.,Ha, S.C.,Kwon, T.,Seo, J.K.,Lee, C.,Rhee, H.W.
Proximity-Directed Labeling Reveals a New Rapamycin-Induced Heterodimer of FKBP25 and FRB in Live Cells
Acs Cent.Sci., 2:506-516, 2016

PubMed Abstract: Mammalian target of rapamycin (mTOR) signaling is a core pathway in cellular metabolism, and control of the mTOR pathway by rapamycin shows potential for the treatment of metabolic diseases. In this study, we employed a new proximity biotin-labeling method using promiscuous biotin ligase (pBirA) to identify unknown elements in the rapamycin-induced interactome on the FK506-rapamycin binding (FRB) domain in living cells. FKBP25 showed the strongest biotin labeling by FRB-pBirA in the presence of rapamycin. Immunoprecipitation and immunofluorescence experiments confirmed that endogenous FKBP25 has a rapamycin-induced physical interaction with the FRB domain. Furthermore, the crystal structure of the ternary complex of FRB-rapamycin-FKBP25 was determined at 1.67-Å resolution. In this crystal structure we found that the conformational changes of FRB generate a hole where there is a methionine-rich space, and covalent metalloid coordination was observed at C2085 of FRB located at the bottom of the hole. Our results imply that FKBP25 might have a unique physiological role related to metallomics in mTOR signaling.

PubMed: 27610411
DOI: 10.1021/acscentsci.6b00137

実験手法

X-RAY DIFFRACTION (1.67 Å)