[PDF][PDF] The structure of a Bcl-xL/Bim fragment complex: implications for Bim function

X Liu, S Dai, Y Zhu, P Marrack, JW Kappler - Immunity, 2003 - cell.com
X Liu, S Dai, Y Zhu, P Marrack, JW Kappler
Immunity, 2003cell.com
After antigen-driven expansion, the majority of T cells involved in an immune response die
rapidly by apoptosis dependent on the Bcl-2 related proteins, Bim and Bax or Bak. The
details of how these proteins are activated and interact are still unclear. The crystal structure
of mouse Bcl-x L bound to a long helical fragment of Bim indicates that the structure of Bim is
very different from proteins with a Bcl-2-like fold and may leave the BH3 region of Bim
constitutively exposed. Based on the structural homology between Bcl-x L and Bax, we …
Abstract
After antigen-driven expansion, the majority of T cells involved in an immune response die rapidly by apoptosis dependent on the Bcl-2 related proteins, Bim and Bax or Bak. The details of how these proteins are activated and interact are still unclear. The crystal structure of mouse Bcl-xL bound to a long helical fragment of Bim indicates that the structure of Bim is very different from proteins with a Bcl-2-like fold and may leave the BH3 region of Bim constitutively exposed. Based on the structural homology between Bcl-xL and Bax, we predicted that binding of Bim to Bax would require displacement of the Bax penultimate α helix. Consistent with this prediction, truncation of this short helix was required for Bim/Bax interaction and led to spontaneous activation of Bax. Our results suggest a way in which both Bim and Bax/Bak might be required for activated T cell apoptosis.
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