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. 2008 Jun 10;6(6):e147. doi: 10.1371/journal.pbio.0060147

Figure 6. Bcl-XL Functions Like a Dominant-Negative Bax.

Figure 6

(A) Cytoplasmic Bax undergoes a conformational change after interacting with membranes (step 1). Interaction of this peripheral membrane (indicated by the shadow) Bax with membrane-bound tBid causes a further conformational change such that Bax integrates in the membrane in an oligomerization competent form (step 2). Conversely, cytoplasmic Bax may interact with other activator proteins to integrate into membranes, or spontaneously active Bax molecules may integrate into the membrane without binding an activator protein. A single tBid molecule activates multiple peripheral membrane Bax molecules, and/or the activated integral membrane Bax recruits more cytoplasmic Bax to the membrane (autoactivation, step 3). Bax oligomerizes.

(B) Bcl-XL exists in a cytoplasmic and/or a peripheral membrane-bound form (step 1). Membrane-bound tBid triggers membrane binding and activation of Bcl-XL (step 2). One tBid molecule can mediate the membrane binding and activation of multiple Bcl-XL molecules (step 3). Bcl-XL does not oligomerize.

(C) Membrane-bound Bcl-XL sequesters tBid and thereby prevents the activation of Bax (step 4). Bcl-XL binds to membrane-bound Bax, preventing Bax oligomerization (step 5) and the recruitment of further peripheral Bax by autoactivation (step 6). In steps 4–6, Bcl-XL functions as a dominant-negative Bax.

(D) Bcl-XL inhibits the conformational change of Bax (step 7, indicated as a change in equilibrium) that is elicited by peripheral membrane binding (step 1 in (A)).