Anti-apoptotic BCL-2 regulation by changes in dynamics of its long unstructured loop

摘要

a Cartoon representation (helices shown as cylinders) of full-length BCL-2. b Cartoon model of the previously reported BCL-2-ΔTM/FLD structure (PDB: 2XA0), exhibiting the ligand-binding groove of BCL-2. The only native cysteine site 158 is clearly away from the binding groove, and thus suitable for conjugating a fluorescence probe. c Cartoon representations of the studied WT and EEE samples, in which the only difference is the phosphomimetic mutations T69E/S70E/S87E. FLD corresponds to the sequence 25–90. d Association of BimBH3 and BCL-2 is examined by FRET. Sequence of BimBH3 peptide is given. BimBH3-AL488 is associated with EEE-PB more potently than with S70E-PB or WT-PB, as compared with other controls (WT-, S70E-, EEE-, BAX136-, cBid87-, T4L99-AL488). Data are shown as mean ± SD (n > 4).