Bcl-xl does not have to bind Bax to protect T cells from death

Abstract

Activated T cells die when antigen disappears from animals. This death is caused by proteins related to Bcl-2. Two hypotheses have been suggested to explain the actions of the different types of Bcl-2 proteins. One hypothesis suggests that, when T cells prepare to die, Bak and Bax, the proteins that actually kill activated T cells, are released from antiapoptotic proteins such as Bcl-2 and Bcl-xl. Another hypothesis suggests that Bak and Bax are normally free and are triggered to kill cells by release of messenger proteins, such as Bim, from Bcl-2 and Bcl-xl. Here, a form of Bcl-xl, which lacks a long unstructured loop, is used to show that the first hypothesis is not correct. Bcl-xl without its loop protects activated T cells from death, yet Bcl-xl without its loop cannot bind any form of Bak and Bax. Thus, binding of Bcl-xl to Bak or Bax is not involved in T cell life or death. The loop of Bcl-xl is also somewhat involved in Bcl-xl's binding of Bim because Bcl-xl without its loop binds Bim less well than wild-type Bcl-xl. Moreover, the loop may have additional, as yet unknown, functions because it changes its shape when Bcl-xl binds Bim.