After Embedding in membranes antiapoptotic bcl-xl protein binds both bcl-2 homology region 3 and helix 1 of proapoptotic bax protein to inhibit apoptotic mitochondrial permeabilization

Jingzhen Ding; Blaine H.M. Mooers; Zhi Zhang; Justin Kale; Domina Falcone; Jamie McNichol; Bo Huang; Xuejun C. Zhang; Chengguo Xing; David W. Andrews; Jialing Lin

doi:10.1074/jbc.M114.552562

After Embedding in membranes antiapoptotic bcl-xl protein binds both bcl-2 homology region 3 and helix 1 of proapoptotic bax protein to inhibit apoptotic mitochondrial permeabilization

Jingzhen Ding, Blaine H.M. Mooers, Zhi Zhang, Justin Kale, Domina Falcone, Jamie McNichol, Bo Huang, Xuejun C. Zhang, Chengguo Xing, David W. Andrews, Jialing Lin

Medicinal Chemistry

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58 Scopus citations

Abstract

Background: Bcl-XL binds Bax at mitochondria, inhibiting Bax oligomerization and apoptosis. Results: Anchored in membranes, Bcl-XL•Bax heterodimer is formed from a rigid helix-in-groove interface plus a flexible helical dimer interface. Conclusion: Two interfaces contribute equally to the heterodimer stability required to inhibit Bax. Significance: This novel kind of protein-protein interaction stabilizes the membrane-bound heterodimer that is pivotal to apoptosis regulation.

Original language	English (US)
Pages (from-to)	11873-11896
Number of pages	24
Journal	Journal of Biological Chemistry
Volume	289
Issue number	17
DOIs	https://doi.org/10.1074/jbc.M114.552562
State	Published - Apr 25 2014

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10.1074/jbc.M114.552562

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Ding, J., Mooers, B. H. M., Zhang, Z., Kale, J., Falcone, D., McNichol, J., Huang, B., Zhang, X. C., Xing, C., Andrews, D. W., & Lin, J. (2014). After Embedding in membranes antiapoptotic bcl-xl protein binds both bcl-2 homology region 3 and helix 1 of proapoptotic bax protein to inhibit apoptotic mitochondrial permeabilization. Journal of Biological Chemistry, 289(17), 11873-11896. https://doi.org/10.1074/jbc.M114.552562

After Embedding in membranes antiapoptotic bcl-xl protein binds both bcl-2 homology region 3 and helix 1 of proapoptotic bax protein to inhibit apoptotic mitochondrial permeabilization. / Ding, Jingzhen; Mooers, Blaine H.M.; Zhang, Zhi et al.

In: Journal of Biological Chemistry, Vol. 289, No. 17, 25.04.2014, p. 11873-11896.

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

Ding, J, Mooers, BHM, Zhang, Z, Kale, J, Falcone, D, McNichol, J, Huang, B, Zhang, XC, Xing, C, Andrews, DW & Lin, J 2014, 'After Embedding in membranes antiapoptotic bcl-xl protein binds both bcl-2 homology region 3 and helix 1 of proapoptotic bax protein to inhibit apoptotic mitochondrial permeabilization', Journal of Biological Chemistry, vol. 289, no. 17, pp. 11873-11896. https://doi.org/10.1074/jbc.M114.552562

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abstract = "Background: Bcl-XL binds Bax at mitochondria, inhibiting Bax oligomerization and apoptosis. Results: Anchored in membranes, Bcl-XL•Bax heterodimer is formed from a rigid helix-in-groove interface plus a flexible helical dimer interface. Conclusion: Two interfaces contribute equally to the heterodimer stability required to inhibit Bax. Significance: This novel kind of protein-protein interaction stabilizes the membrane-bound heterodimer that is pivotal to apoptosis regulation.",

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AU - Mooers, Blaine H.M.

AU - Zhang, Zhi

AU - Kale, Justin

AU - Falcone, Domina

AU - McNichol, Jamie

AU - Huang, Bo

AU - Zhang, Xuejun C.

AU - Xing, Chengguo

AU - Andrews, David W.

AU - Lin, Jialing

PY - 2014/4/25

Y1 - 2014/4/25

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After Embedding in membranes antiapoptotic bcl-xl protein binds both bcl-2 homology region 3 and helix 1 of proapoptotic bax protein to inhibit apoptotic mitochondrial permeabilization

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