Structural basis for the interaction between DJ-1 and Bcl-XL

Mi Kyung Lee; Min Sung Lee; Da Woon Bae; Dong Hwa Lee; Sun Shin Cha; Seung Wook Chi

doi:10.1016/j.bbrc.2017.11.129

Structural basis for the interaction between DJ-1 and Bcl-X_L

Mi Kyung Lee, Min Sung Lee, Da Woon Bae, Dong Hwa Lee, Sun Shin Cha, Seung Wook Chi

Department of Chemistry & Nanoscience

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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-X_L protects cells against death. In this study, we characterized the molecular interaction between DJ-1 and Bcl-X_L 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-X_L. 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-X_L and, thus, acts as a Bcl-X_L-binding motif. In combination with the NMR chemical shift perturbation data, a refined structural model of the Bcl-X_L/DJ-1 Cpep complex revealed that the binding mode is remarkably similar to that of other Bcl-X_L/pro-apoptotic BH3 peptide complexes. Taken together, our results provide a structural basis for the binding mechanism between DJ-1 and Bcl-X_L, which will contribute to molecular understanding of the role of mitochondrial DJ-1 in Bcl-X_L regulation in response to oxidative stress.

Original language	English
Pages (from-to)	1067-1073
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	495
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2017.11.129
State	Published - 1 Jan 2018

Bibliographical 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:
© 2017 Elsevier Inc.

Keywords

Bcl-X
Complex structure
DJ-1
NMR spectroscopy
Protein interaction

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10.1016/j.bbrc.2017.11.129

Cite this

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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.",

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T1 - Structural basis for the interaction between DJ-1 and Bcl-XL

AU - Lee, Mi Kyung

AU - Lee, Min Sung

AU - Bae, Da Woon

AU - Lee, Dong Hwa

AU - Cha, Sun Shin

AU - Chi, Seung Wook

N1 - 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: © 2017 Elsevier Inc.

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N2 - 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.

AB - 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.

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