Unknown

Dataset Information

0

Structural transition in Bcl-xL and its potential association with mitochondrial calcium ion transport.


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 ?-D-Maltoside (OM). The detergent-treated Bcl-xL forms a dimer through three-dimensional domain swapping (3DDS) by swapping helices ?6-?8 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.

SUBMITTER: Rajan S 

PROVIDER: S-EPMC4448555 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Structural transition in Bcl-xL and its potential association with mitochondrial calcium ion transport.

Rajan Sreekanth S   Choi Minjoo M   Nguyen Quoc Toan QT   Ye Hong H   Liu Wei W   Toh Hui Ting HT   Kang CongBao C   Kamariah Neelagandan N   Li Chi C   Huang Huiya H   White Carl C   Baek Kwanghee K   Grüber Gerhard G   Yoon Ho Sup HS  

Scientific reports 20150529


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 (3DD  ...[more]

Similar Datasets

| S-EPMC3198165 | biostudies-literature
| S-EPMC6540150 | biostudies-literature
| S-EPMC5635221 | biostudies-literature
| S-EPMC2579276 | biostudies-literature
| S-EPMC1162412 | biostudies-other
| S-EPMC6724524 | biostudies-literature
| S-EPMC2653056 | biostudies-literature
| S-EPMC1161720 | biostudies-other
| S-EPMC4746289 | biostudies-literature
| S-EPMC2924085 | biostudies-literature