Sequence-specific Dimerization of the Transmembrane Domain of the “BH3-only” Protein BNIP3 in Membranes and Detergent

摘要: Mitochondria-mediated apoptosis is regulated by proteins of the Bcl-2 superfamily, most which contain a C-terminal hydrophobic domain that plays role in membrane targeting. Experiments with BNIP3 have implicated transmembrane (TM) its proapoptotic function, homodimerization, and interactions Bcl-xL. We show TM self-associates strongly Escherichia coli cell membranes causes reversible dimerization soluble protein detergent SDS when expressed as an in-frame fusion. Limited mutational analysis identifies specific residues are critical for self-association membranes, these also important micelles, suggesting observed preserved detergent. The effects sequence changes at positions Ala176 Gly180 suggest associates using variant GXXXG motif previously shown to be glycophorin A. importance residue His173 indicates polar residues, been model peptides, can act concert AXXXG stabilize interactions. Our results demonstrate pro-apoptotic dimerizes tightly lipidic environments, this association has strong dependence but independent identity flanking regions. Thus, represents another region superfamily capable mediating protein-protein