5GPG
Co-crystal structure of the FK506 binding domain of human FKBP25, Rapamycin and the FRB domain of human mTOR
Summary for 5GPG
| Entry DOI | 10.2210/pdb5gpg/pdb |
| Descriptor | Peptidyl-prolyl cis-trans isomerase FKBP3, Serine/threonine-protein kinase mTOR, RAPAMYCIN IMMUNOSUPPRESSANT DRUG, ... (4 entities in total) |
| Functional Keywords | complex, kinase, isomerase-transferase complex, isomerase/transferase |
| Biological source | Homo sapiens (Human) More |
| Cellular location | Nucleus: Q00688 Endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side : P42345 |
| Total number of polymer chains | 2 |
| Total formula weight | 25314.00 |
| Authors | Lee, H.B.,Lee, S.Y.,Rhee, H.W.,Lee, C.W. (deposition date: 2016-08-02, release date: 2016-10-12, Last modification date: 2023-11-08) |
| Primary citation | 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 Cited by 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: 27610411DOI: 10.1021/acscentsci.6b00137 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.67 Å) |
Structure validation
Download full validation report
