Structural basis for the interaction between DJ-1 and Bcl-XL
- Disease Target Structure Research Center, KRIBB, Daejeon 34141 (Korea, Republic of)
- Department of Chemistry & Nanoscience, Ewha Womans University, Seoul 03760 (Korea, Republic of)
Highlights: • Oxidized, but not reduced, DJ-1 interacts with Bcl-X{sub L}. • C-terminal α8-helix of DJ-1 acts as a binding motif for Bcl-X{sub L}. • C-terminal α8-helix of DJ-1 binds to the BH3 peptide-binding groove in Bcl-X{sub L}. • A conserved binding mode of the Bcl-X{sub L}/DJ-1 and other Bcl-X{sub L}/BH3 peptide complexes. • Understanding of structural basis for the binding between DJ-1 and Bcl-X{sub L}. 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{sub L} protects cells against death. In this study, we characterized the molecular interaction between DJ-1 and Bcl-X{sub 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{sub 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{sub L} and, thus, acts as a Bcl-X{sub L}-binding motif. In combination with the NMR chemical shift perturbation data, a refined structural model of the Bcl-X{sub L}/DJ-1 Cpep complex revealed that the binding mode is remarkably similar to that of other Bcl-X{sub L}/pro-apoptotic BH3 peptide complexes. Taken together, our results provide a structural basis for the binding mechanism between DJ-1 and Bcl-X{sub L}, which will contribute to molecular understanding of the role of mitochondrial DJ-1 in Bcl-X{sub L} regulation in response to oxidative stress.
- OSTI ID:
- 23134457
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 495; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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