Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/105691
Title: Structural transition in Bcl-xL and its potential association with mitochondrial calcium ion transport
Authors: Rajan, Sreekanth
Choi, Minjoo
Nguyen, Quoc Toan
Ye, Hong
Liu, Wei
Toh, Hui Ting
Kang, CongBao
Kamariah, Neelagandan
Li, Chi
Huang, Huiya
White, Carl
Baek, Kwanghee
Grüber, Gerhard
Yoon, Ho Sup
Keywords: DRNTU::Science::Biological sciences
Issue Date: 2015
Source: Rajan, S., Choi, M., Nguyen, Q. T., Ye, H., Liu, W., Toh, H. T., et al. (2015). Structural transition in Bcl-xL and its potential association with mitochondrial calcium ion transport. Scientific Reports, 5, 10609-.
Series/Report no.: Scientific Reports
Abstract: Bcl-2 family proteins are key regulators for cellular homeostasis in response to apoptotic stimuli. Bcl-xL, an antiapoptotic Bcl-2 family member, undergoes conformational transitions, which leads to two conformational states: the cytoplasmic and membrane-bound. Here we present the crystal and small-angle X-ray scattering (SAXS) structures of Bcl-xL treated with the mild detergent n-Octyl β-D-Maltoside (OM). The detergent-treated Bcl-xL forms a dimer through three-dimensional domain swapping (3DDS) by swapping helices α6-α8 between two monomers. Unlike Bax, a proapoptotic member of the Bcl-2 family, Bcl-xL is not converted to 3DDS homodimer upon binding BH3 peptides and ABT-737, a BH3 mimetic drug. We also designed Bcl-xL mutants which cannot dimerize and show that these mutants reduced mitochondrial calcium uptake in MEF cells. This illustrates the structural plasticity in Bcl-xL providing hints toward the probable molecular mechanism for Bcl-xL to play a regulatory role in mitochondrial calcium ion transport.
URI: https://hdl.handle.net/10356/105691
http://hdl.handle.net/10220/26043
ISSN: 2045-2322
DOI: 10.1038/srep10609
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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