Structure assembly of Bcl-xL through α5-α5 and α6-α6 interhelix interactions in lipid membranes

Citations of this article
Mendeley users who have this article in their library.


Lipid bilayer membrane is the main site where Bcl-xL executes its anti-apoptotic function. Here we used site-directed mutagenesis and cysteine-directed cross-linking to trap the structure of Bcl-xL upon membrane insertion. Cys151 on α5-helix and Asn185 on α6-helix of two neighboring Bcl-xL are found in close positions, respectively. The FRET based binding assay indicated that the BH3-peptide binding pocket in Bcl-xL is disrupted after its membrane insertion. Co-immunoprecipitation experiments showed that the membrane-bound Bcl-xL sequestered tBid by direct interaction at physiological pH. If Bcl-xL behaves similarly at low pH as it does at physiological pH, the membrane-bound Bcl-xL should bind to tBid through protein regions other than the BH3 domain of tBid and the hydrophobic pocket of Bcl-xL. Previously, a crystallography study demonstrated that Bcl-xL formed homodimers through domain swapping in water, where Cys151 and Asn185 of two monomeric subunits are far apart from each other and the BH3-peptide binding pocket is intact. Our results indicated that Bcl-xL dimer trapped by cross-linking in lipids is distinct from the domain swapped dimer, suggesting that Bcl-xL transits through a structural change from the water-soluble state to the membrane-bound state and there are multiple possibilities for structural reorganization of Bcl-xL protein. © 2009 Elsevier B.V. All rights reserved.




Feng, Y., Liu, D., Shen, X., Chen, K., & Jiang, H. (2009). Structure assembly of Bcl-xL through α5-α5 and α6-α6 interhelix interactions in lipid membranes. Biochimica et Biophysica Acta - Biomembranes, 1788(11), 2389–2395.

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free