Bcl-xl does not have to bind Bax to protect T cells from death.
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.
Liu
Xinqi
X
Howard Hughes Medical Institute and Integrated Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Zhu
Yanan
Y
Dai
Shaodong
S
White
Janice
J
Peyerl
Fred
F
Kappler
John W
JW
Marrack
Philippa
P
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D002460:Cell Line; D018360:Crystallography, X-Ray; D004768:Enterotoxins / Q000276:immunology; D047468:Immunoprecipitation; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D009154:Mutation; D010447:Peptide Hydrolases / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D014162:Transfection; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051020:bcl-X Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; C494773:Bak1 protein, mouse; C494827:Bax protein, mouse; D000072224:Bcl-2-Like Protein 11; C494812:Bcl2l1 protein, mouse; C000606776:Bcl2l11 protein, mouse; D004768:Enterotoxins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; C031818:enterotoxin B, staphylococcal; D010447:Peptide Hydrolases