Journal of Biochemistry Advance Access published online on November 15, 2007
Journal of Biochemistry, doi:10.1093/jb/mvm216
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© 2007 The Japanese Biochemical Society
Bcl-xL Forms Two Distinct Homodimers At Non-Ionic Detergents: Implications In The Dimerization of Bcl-2 Family Proteins
1 Department of Molecular Pharmacology; 2 Center for Drug Design and Discovery, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica,Chinese Academy of Sciences, Shanghai 201203, China, 3 School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
*To whom correspondence should be addressed: 555 Zu-Chong-Zhi Road, Shanghai 201203, China Email: dxl{at}mail.shcnc.ac.cn; Phone: +86-21-50806600; Fax: +86-21-50806065
Received October 29, 2007; Accepted October 31, 2007
| Abstract |
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As the key regulator of apoptosis, Bcl-2 family protein controls the cell death by forming homo- or heterodimers among anti-apoptotic and pro-apoptotic members of this family. Here we have studied Bcl-xL homodimerization at different pH in the presence of various detergents and organic solvents. We found that both acidic and basic pH are beneficial for Bcl-xL dimerization. High concentrations of non-ionic detergents and some organic solvents can significantly promote this event. In addition to non-covalently linked acidic-dimer as that formed at acidic pH, Bcl-xL formed disulfide-bonded detergent-dimer at neutral and basic pH when incubated with high concentrations of non-ionic detergents. The acidic-dimer retains the BH3 peptide binding activity whereas the detergent-dimer does not. The formation of acidic-dimer and detergent-dimer implies that Bcl-xL may dimerize via two different pathways under certain conditions. The implications of these findings has been discussed with previous experimental results, which provides some new insight into the events and would help the experiment design and data interpretation when non-ionic detergents are used to study the dimerization and pore formation of Bcl-2 family proteins.
Key Words: Apoptosis, Bcl-2 family protein, Dimerization, Domain swapping, Non-Ionic detergent