Bax does not have to adopt its final form to drive T cell death.
The introduction of antigen into animals causes antigen-specific T cells to divide and then die. Activated T cell death requires either of the death effector molecules, Bak or Bax. When T cells die, Bak and Bax change their conformations, a phenomenon that is thought to be required for Bak or Bax to drive cell death. Here we show that Bak changes conformation before activated T cells die, as detected by an antibody specific for a peptide near the NH2 terminus of Bak, but Bax does not change its shape markedly until after the cells are dead, as detected by an antibody specific for a peptide near the NH2 terminus of Bax. This latter finding is also true in activated T cells that lack Bak and are therefore dependent on Bax to die. This result suggests that Bax does not have to adopt its final, completely unfolded form until after the cells are dead.
Zhu
Yanan
Y
Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center, Denver, CO 80220, USA.
Liu
Xinqi
X
Hildeman
David
D
Peyerl
Fred W
FW
White
Janice
J
Kushnir
Elenora
E
Kappler
John
J
Marrack
Philippa
P
D000818:Animals; D016923:Cell Death / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D011487:Protein Conformation; D017510:Protein Folding; D013601:T-Lymphocytes / Q000276:immunology*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000172:deficiency / Q000276:immunology*; D051028:bcl-2-Associated X Protein / Q000276:immunology*
C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein