4PPI

Crystal structure of Bcl-xL hexamer

Summary for 4PPI

• Entry DOI: 10.2210/pdb4ppi/pdb
• Descriptor: Bcl-2-like protein 1, GLYCEROL (3 entities in total)
• Functional Keywords: 3d domain swap, apoptosis, anti-apoptotic, bcl-2 family
• Biological source: Homo sapiens (human)
• Cellular location: Isoform Bcl-X(L): Mitochondrion inner membrane : Q07817
• Total number of polymer chains: 1
• Total formula weight: 19405.31

Authors

Sreekanth, R.,Yoon, H.S. (deposition date: 2014-02-27, release date: 2015-03-04, Last modification date: 2023-11-08)

Primary citation

Rajan, S.,Choi, M.,Nguyen, Q.T.,Ye, H.,Liu, W.,Toh, H.T.,Kang, C.,Kamariah, N.,Li, C.,Huang, H.,White, C.,Baek, K.,Gruber, G.,Yoon, H.S.
Structural transition in Bcl-xL and its potential association with mitochondrial calcium ion transport
Sci Rep, 5:10609-10609, 2015

PubMed 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.

PubMed: 26023881
DOI: 10.1038/srep10609

Experimental method

X-RAY DIFFRACTION (2.851 Å)