A Structural Model for Bax∆2-Mediated Activation of Caspase 8-Dependent Apoptosis
Abstract
:1. Introduction
2. Results
2.1. Bax Variants Are Predicted to Have Distinct Structures
2.2. Helix α9 May Be Involved in Bax∆2-Caspase 8 Docking
3. Discussion
4. Materials and Methods
4.1. Protein Sequences
4.2. Homology Modeling
4.3. Molecular Dynamics Simulation
4.4. Analysis of MD Simulation
4.5. Protein–Protein Docking
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Sen, S. Programmed cell death: Concept, mechanism and control. Biol. Rev. 1992, 67, 287–319. [Google Scholar] [CrossRef] [PubMed]
- Fuchs, Y.; Steller, H. Programmed cell death in animal development and disease. Cell 2011, 147, 742–758. [Google Scholar] [CrossRef] [Green Version]
- Chen, M.; Wang, J. Initiator caspases in apoptosis signaling pathways. Apoptosis 2002, 7, 313–319. [Google Scholar] [CrossRef] [PubMed]
- Zhao, Y.; Sui, X.; Hong, R. From procaspase-8 to caspase-8: Revisiting structural functions of caspase-8. J. Cell. Physiol. 2010, 225, 316–320. [Google Scholar] [CrossRef] [PubMed]
- Dickens, L.S.; Boyd, R.S.; Jukes-Jones, R.; Hughes, M.A.; Robinson, G.L.; Fairall, L.; Schwabe, J.W.R.; Cain, K.; MacFarlane, M. A Death effector domain chain disc model reveals a crucial role for caspase-8 chain assembly in mediating apoptotic cell death. Mol. Cell 2012, 47, 291–305. [Google Scholar] [CrossRef] [Green Version]
- Jürgensmeier, J.M.; Xie, Z.; Deveraux, Q.; Ellerby, L.; Bredesen, D.; Reed, J.C. Bax directly induces release of cytochrome c from isolated mitochondria. Proc. Natl. Acad. Sci. USA 1998, 95, 4997–5002. [Google Scholar] [CrossRef] [Green Version]
- Pawlowski, J.; Kraft, A.S. Bax-induced apoptotic cell death. Proc. Natl. Acad. Sci. USA 2000, 97, 529–531. [Google Scholar] [CrossRef] [Green Version]
- Brentnall, M.; Rodriguez-Menocal, L.; De Guevara, R.L.; Cepero, E.; Boise, L.H. Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol. 2013, 14, 32. [Google Scholar] [CrossRef] [Green Version]
- Takeuchi, O.; Fisher, J.; Suh, H.; Harada, H.; Malynn, B.A.; Korsmeyer, S.J. Essential role of BAX, BAK in B cell homeostasis and prevention of autoimmune disease. Proc. Natl. Acad. Sci. USA 2005, 102, 11272–11277. [Google Scholar] [CrossRef] [Green Version]
- Perier, C.; Bové, J.; Wu, D.C.; Dehay, B.; Choi, D.K.; Jackson-Lewis, V.; Rathke-Hartlieb, S.; Bouillet, P.; Strasser, A.; Schulz, J.B.; et al. Two molecular pathways initiate mitochondria-dependent dopaminergic neurodegeneration in experimental Parkinson’s disease. Proc. Natl. Acad. Sci. USA 2007, 104, 8161–8166. [Google Scholar] [CrossRef] [Green Version]
- Obulesu, M.; Lakshmi, M.J. Apoptosis in Alzheimer’s disease: An understanding of the physiology, pathology and therapeutic avenues. Neurochem. Res. 2014, 39, 2301–2312. [Google Scholar] [CrossRef] [PubMed]
- Zhou, M.; Demo, S.D.; McClure, T.N.; Crea, R.; Bitler, C.M. A novel splice variant of the cell death-promoting protein BAX. J. Biol. Chem. 1998, 273, 11930–11936. [Google Scholar] [CrossRef] [Green Version]
- Jin, K.L.; Graham, S.H.; Mao, X.O.; He, X.; Nagayama, T.; Simon, R.P.; Greenberg, D.A. Bax κ, a novel Bax splice variant from ischemic rat brain lacking an ART domain, promotes neuronal cell death. J. Neurochem. 2001, 77, 1508–1519. [Google Scholar] [CrossRef] [PubMed]
- Haferkamp, B.; Zhang, H.; Lin, Y.; Yeap, X.; Bunce, A.; Sharpe, J.; Xiang, J. BaxΔ2 is a novel bax isoform unique to microsatellite unstable tumors. J. Biol. Chem. 2012, 287, 34722–34729. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cartron, P.F.; Moreau, C.; Oliver, L.; Mayat, E.; Meflah, K.; Vallette, F.M. Involvement of the N-terminus of Bax in its intracellular localization and function. FEBS Lett. 2002, 512, 95–100. [Google Scholar] [CrossRef] [Green Version]
- Sani, M.A.; Dufourc, E.J.; Gröbner, G. How does the Bax-α1 targeting sequence interact with mitochondrial membranes? The role of cardiolipin. Biochim. Biophys. Acta-Biomembr. 2009, 1788, 623–631. [Google Scholar] [CrossRef] [Green Version]
- George, N.M.; Targy, N.; Evans, J.J.D.; Zhang, L.; Luo, X. Bax contains two functional mitochondrial targeting sequences and translocates to mitochondria in a conformational change- and homo-oligomerization-driven process. J. Biol. Chem. 2010, 285, 1384–1392. [Google Scholar] [CrossRef] [Green Version]
- Liao, C.; Zhang, Z.; Kale, J.; Andrews, D.W.; Lin, J.; Li, J. Conformational heterogeneity of bax helix 9 dimer for apoptotic pore formation. Sci. Rep. 2016, 6, 29502. [Google Scholar] [CrossRef] [Green Version]
- Zhang, H.; Lin, Y.; Mañas, A.; Zhao, Y.; Denning, M.F.; Ma, L.; Xiang, J. Baxδ2 promotes apoptosis through caspase-8 activation in microsatellite-unstable colon cancer. Mol. Cancer Res. 2014, 12, 1225–1232. [Google Scholar] [CrossRef] [Green Version]
- Mañas, A.; Chen, W.; Nelson, A.; Yao, Q.; Xiang, J. BaxΔ2 sensitizes colorectal cancer cells to proteasome inhibitor-induced cell death. Biochem. Biophys. Res. Commun. 2018, 496, 18–24. [Google Scholar] [CrossRef]
- Mañas, A.; Wang, S.; Nelson, A.; Li, J.; Zhao, Y.; Zhang, H.; Davis, A.; Xie, B.; Maltsev, N.; Xiang, J. The functional domains for Bax∆2 aggregate-mediated caspase 8-dependent cell death. Exp. Cell Res. 2017, 359, 342–355. [Google Scholar] [CrossRef] [PubMed]
- Haferkamp, B.; Zhang, H.; Kissinger, S.; Wang, X.; Lin, Y.; Schultz, M.; Xiang, J. BaxΔ2 family alternative splicing salvages bax microsatellite-frameshift mutations. Genes Cancer 2013, 4, 501–512. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shen, C.; Pei, J.; Guo, X.; Zhou, L.; Li, Q.; Quan, J. Structural basis for dimerization of the death effector domain of the F122A mutant of Caspase-8. Sci. Rep. 2018, 8, 1–10. [Google Scholar]
- Petersen, B.; Petersen, T.N.; Andersen, P.; Nielsen, M.; Lundegaard, C. A generic method for assignment of reliability scores applied to solvent accessibility predictions. BMC Struct. Biol. 2009, 9, 51. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Garnier, J.; Gibrat, J.F.; Robson, B. GOR method for predicting protein secondary structure from amino acid sequence. Methods Enzymol. 1996, 266, 540–553. [Google Scholar]
- Tsapras, P.; Nezis, I.P. Caspase involvement in autophagy. Cell Death Differ. 2017, 241, 369–1379. [Google Scholar] [CrossRef] [Green Version]
- Renault, T.T.; Floros, K.V.; Elkholi, R.; Corrigan, K.A.; Kushnareva, Y.; Wieder, S.Y.; Lindtner, C.; Serasinghe, M.N.; Asciolla, J.J.; Buettner, C.; et al. Mitochondrial shape governs BAX-induced membrane permeabilization and apoptosis. Mol. Cell 2015, 57, 69–82. [Google Scholar] [CrossRef] [Green Version]
- Zhang, M.; Zheng, J.; Nussinov, R.; Ma, B. Release of cytochrome C from bax pores at the mitochondrial membrane. Sci. Rep. 2017, 7, 1–13. [Google Scholar] [CrossRef]
- Hancock, J.M.; Zvelebil, M.J.; Griffith, M.; Griffith, O.L. RefSeq (the Reference Sequence Database). Dict. Bioinform. Comput. Biol. 2004, 33, D501–D504. [Google Scholar]
- Källberg, M.; Margaryan, G.; Wang, S.; Ma, J.; Xu, J. Raptorx server: A resource for template-based protein structure modeling. Methods Mol. Biol. 2014, 1137, 17–27. [Google Scholar]
- Webb, B.; Sali, A. Comparative protein structure modeling using MODELLER. Curr. Protoc. Bioinform. 2016, 54, 5–6. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rohl, C.A.; Strauss, C.E.M.; Misura, K.M.S.; Baker, D. Protein structure prediction using rosetta. Methods Enzymol. 2004, 383, 66–93. [Google Scholar] [PubMed]
- Eastman, P.; Swails, J.; Chodera, J.D.; McGibbon, R.T.; Zhao, Y.; Beauchamp, K.A.; Wang, L.P.; Pande, V.S. OpenMM 7: Rapid development of high performance algorithms for molecular dynamics. PLoS Comput. Biol. 2017, 13, e1005659. [Google Scholar] [CrossRef] [PubMed]
- Cook, E.; Smith, M. The University of California Pay It Forward Open Access Publishing Research Project: An Interview with MacKenzie Smith. Ser. Libr. 2017, 73, 1–4. [Google Scholar] [CrossRef] [Green Version]
- Bakan, A.; Meireles, L.M.; Bahar, I. ProDy: Protein dynamics inferred from theory and experiments. Bioinformatics 2011, 27, 1575–1577. [Google Scholar] [CrossRef] [Green Version]
- Humphrey, W.; Dalke, A.; Schulten, K. VMD: Visual molecular dynamics. J. Mol. Graph. 1996, 14, 33–38. [Google Scholar] [CrossRef]
- Virtanen, P.; Gommers, R.; Oliphant, T.E.; Haberland, M.; Reddy, T.; Cournapeau, D.; Burovski, E.; Peterson, P.; Weckesser, W.; Bright, J.; et al. SciPy 1.0: Fundamental algorithms for scientific computing in Python. Nat. Methods 2020, 17, 261–272. [Google Scholar] [CrossRef] [Green Version]
- Pedregosa, F.; Varoquaux, G.; Gramfort, A.; Michel, V.; Thirion, B.; Grisel, O.; Blondel, M.; Prettenhofer, P.; Weiss, R.; Duchesnay, É. Scikit-learn: Machine learning in Python. J. Mach. Learn. Res. 2011, 12, 2825–2830. [Google Scholar]
- Chaudhury, S.; Lyskov, S.; Gray, J.J. PyRosetta: A script-based interface for implementing molecular modeling algorithms using Rosetta. Bioinformatics 2010, 26, 689–691. [Google Scholar] [CrossRef]
2nd Structure | Baxα Baxα[L26P/L27P] | Bax∆2 Bax∆2[L164P] |
---|---|---|
Loop | 1–15 | 1–36 |
Helix α1 | 16–35 | - |
Helix α2 | 54–72 | 37–55 |
Helix α3 | 74–82 | 57–65 |
Helix α4 | 88–100 | 71–83 |
Helix α5 | 108–127 | 91–110 |
Helix α6 | 130–146 | 113–129 |
Helix α7 | 148–154 | 131–137 |
Helix α8 | 158–164 | 141–147 |
Helix α9 | 171–188 | 154–171 |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Xie, B.; Yao, Q.; Xiang, J.; Minh, D.D.L. A Structural Model for Bax∆2-Mediated Activation of Caspase 8-Dependent Apoptosis. Int. J. Mol. Sci. 2020, 21, 5476. https://doi.org/10.3390/ijms21155476
Xie B, Yao Q, Xiang J, Minh DDL. A Structural Model for Bax∆2-Mediated Activation of Caspase 8-Dependent Apoptosis. International Journal of Molecular Sciences. 2020; 21(15):5476. https://doi.org/10.3390/ijms21155476
Chicago/Turabian StyleXie, Bing, Qi Yao, Jialing Xiang, and David D.L. Minh. 2020. "A Structural Model for Bax∆2-Mediated Activation of Caspase 8-Dependent Apoptosis" International Journal of Molecular Sciences 21, no. 15: 5476. https://doi.org/10.3390/ijms21155476