title: Bcl-xL forms two distinct homodimers at non-ionic detergents: implications in the dimerization of Bcl-2 family proteins.
abstract: 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-x(L) homodimerization at different pH in the presence of various detergents and organic solvents. We found that both acidic and basic pHs are beneficial for Bcl-x(L) 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-x(L) formed disulphide-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-x(L) 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.
authors.affiliation: Department of Molecular Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Feng
authors.forename: Zhaohu
authors.initials: Z
authors.lastname: Lin
authors.forename: Xu
authors.initials: X
authors.lastname: Shen
authors.forename: Kaixian
authors.initials: K
authors.lastname: Chen
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Dongxiang
authors.initials: D
authors.lastname: Liu
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D003902:Detergents / Q000737:chemistry*; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D051020:bcl-X Protein / Q000737:chemistry*
chemical_list: D017931:DNA Primers; D003902:Detergents; D051020:bcl-X Protein