Figure 3.

Binding of BH3 peptides to the groove and rear pocket of Bax promotes conformation change and oligomerization. Cartoon and surface overlays of Bax structures and models that support the transitions of Bax and Bak are described in Figure 2. Color scheme of the helices as in Figure 2. (a) NMR structure of the full-length Bax monomer (1F16). Note, the locations of the hydrophobic surface groove, rear pocket, BH3 domain and TM are indicated. (b) Model of a BimBH3 peptide (magenta tube) bound to the rear pocket of full-length Bax calculated from NMR data. Note that binding of the BimBH3 peptide displaced the α1/α2 loop (red arrow). BimBH3 binding coincided with the exposure of the N-terminal 6A7 epitope (marked in yellow), α9 helix and the BH3 domain (black arrows). (c) Crystal structure of a BidBH3 peptide (magenta tube) bound to the groove of BaxΔC21 (4BD2). Note that BidBH3 peptide binding induced partial α2 displacement (short red arrow) and dissociation of the C-terminal α6–α8 helices (latch) from the N-terminal α1–α5 helices (core) (long red arrow). (d) Crystal structure of the α2–α5 Bax ‘core' forming a BH3:groove dimer (4BDU). Note that aromatic residues (dark gray) on helices α4 and α5 form a lipophilic surface. Although the lipophilic surface is concave in the homodimer structure, whether this curvature is retained when Bax is associated with the MOM and whether the curvature is important for membrane permeabilization is unknown. (e) Overlay of the Bax:BidBH3 complex (colored:magenta, from c) with one half of the Bax BH3:groove dimer (in gray, from d). Note, to form the BH3:groove dimer, no major rearrangements of the ‘core' helices occur other than the exposure of the BH3 domain (α2, red arrow)