7F2J

Crystal structure of AtFKBP53 FKBD in complex with rapamycin

Summary for 7F2J

• Entry DOI: 10.2210/pdb7f2j/pdb
• Related: 6J2M
• Descriptor: Peptidyl-prolyl cis-trans isomerase FKBP53, RAPAMYCIN IMMUNOSUPPRESSANT DRUG, SULFATE ION, ... (5 entities in total)
• Functional Keywords: fkbp, rapamycin, dimerization, isomerase
• Biological source: Arabidopsis thaliana (Mouse-ear cress)
• Total number of polymer chains: 2
• Total formula weight: 29712.25

Authors

Singh, A.K.,Saharan, K.,Vasudevan, D. (deposition date: 2021-06-11, release date: 2022-03-09, Last modification date: 2023-11-29)

Primary citation

Singh, A.K.,Saharan, K.,Baral, S.,Luan, S.,Vasudevan, D.
Crystal packing reveals rapamycin-mediated homodimerization of an FK506-binding domain.
Int.J.Biol.Macromol., 206:670-680, 2022

PubMed Abstract: Chemically induced dimerization (CID) is used to induce proximity and result in artificial complex formation between a pair of proteins involved in biological processes in cells to investigate and regulate these processes. The induced heterodimerization of FKBP fusion proteins by rapamycin and FK506 has been extensively exploited as a chemically induced dimerization system to regulate and understand highly dynamic cellular processes. Here, we report the crystal structure of the AtFKBP53 FKBD in complex with rapamycin. The crystal packing reveals an unusual feature whereby two rapamycin molecules appear to mediate homodimerization of the FKBD. The triene arm of rapamycin appears to play a significant role in forming this dimer. This forms the first structural report of rapamycin-mediated homodimerization of an FKBP. The structural information on the rapamycin-mediated FKBD dimerization may be employed to design and synthesize covalently linked dimeric rapamycin, which may subsequently serve as a chemically induced dimerization system for the regulation and characterization of cellular processes.

PubMed: 35218805
DOI: 10.1016/j.ijbiomac.2022.02.107

Experimental method

X-RAY DIFFRACTION (1.6 Å)