@article{1db2f34da9064e6d8c7b00f7ec9e9fdb,
title = "Structural basis for the interaction between DJ-1 and Bcl-XL",
abstract = "DJ-1 is a multifunctional protein associated with Parkinson's disease (PD) and tumorigenesis. In response to ultraviolet B (UVB) irradiation, DJ-1 is translocated into the mitochondria, and its interaction with the mitochondrial protein Bcl-XL protects cells against death. In this study, we characterized the molecular interaction between DJ-1 and Bcl-XL by NMR spectroscopy. The NMR chemical shift perturbation data demonstrated that the oxidized but not the reduced form of DJ-1 binds to the predominantly hydrophobic groove surrounded by the BH1–BH3 domains in Bcl-XL. In addition, our results showed that the C-terminal α8-helix peptide (Cpep) of DJ-1 binds to the pro-apoptotic BH3 peptide-binding hydrophobic groove in Bcl-XL and, thus, acts as a Bcl-XL-binding motif. In combination with the NMR chemical shift perturbation data, a refined structural model of the Bcl-XL/DJ-1 Cpep complex revealed that the binding mode is remarkably similar to that of other Bcl-XL/pro-apoptotic BH3 peptide complexes. Taken together, our results provide a structural basis for the binding mechanism between DJ-1 and Bcl-XL, which will contribute to molecular understanding of the role of mitochondrial DJ-1 in Bcl-XL regulation in response to oxidative stress.",
keywords = "Bcl-X, Complex structure, DJ-1, NMR spectroscopy, Protein interaction",
author = "Lee, {Mi Kyung} and Lee, {Min Sung} and Bae, {Da Woon} and Lee, {Dong Hwa} and Cha, {Sun Shin} and Chi, {Seung Wook}",
note = "Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (MEST, NRF-2012M3C1A3671508 and NRF-2017R1A2B4006378 ) and the Bio-Synergy Research Project of the Ministry of Science, ICT, and Future Planning through the National Research Foundation ( NRF-2015M3A9C4076320 ). This work was also supported by the KRIBB Research Initiative Program. S.-S. Cha was supported by the project titled “Development of biomedical materials based on marine proteins,” funded by the Ministry of Oceans and Fisheries, Korea . Funding Information: This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (MEST, NRF-2012M3C1A3671508 and NRF-2017R1A2B4006378) and the Bio-Synergy Research Project of the Ministry of Science, ICT, and Future Planning through the National Research Foundation (NRF-2015M3A9C4076320). This work was also supported by the KRIBB Research Initiative Program. S.-S. Cha was supported by the project titled ?Development of biomedical materials based on marine proteins,? funded by the Ministry of Oceans and Fisheries, Korea. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2018",
month = jan,
day = "1",
doi = "10.1016/j.bbrc.2017.11.129",
language = "English",
volume = "495",
pages = "1067--1073",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Academic Press Inc.",
number = "1",
}