Oligomerization of BH4-truncated Bcl-XL in solution

BH4 domain is critical for the anti-apoptotic functions of Bcl-2 and Bcl-x(L) and their binding abilities with other members of the Bcl-2 family. The cleavage of the BH4 domain in Bcl-x(L) and Bcl-2 by caspase 1 or 3 converts the anti-apoptotic Bcl-x(L) and Bcl-2 into proapoptotic proteins that potently induce apoptosis. Herein, we report that recombinant BCl-x(L) proteins without N-terminal 61 residues, His(6)-N Delta 6l-BCl-x(L)-C Delta 21 and N Delta 61-BCl-x(L)-C Delta 21, form oligomers in solution, whereas Bcl-x(L)-C Delta 21 exists as a monomer. The oligomerization of the truncated proteins is independent of protein-lipid interaction, protein concentration or the ion strength of the solution. Circular dichroism spectrum shows a significant decrease in the content of alpha-helices upon deletion of N-terminal residues. N Delta 61-Bcl-x(L)-C Delta 21 also loses its heterodimerization capability with the BH3 peptide derived from Bak. This newly acquired property might be linked to its ability to induce apoptosis in cells. (C) 2007 Elsevier Inc. All rights reserved.