Related Experiment Videos
The structure of a Bcl-xL/Bim fragment complex: implications for Bim function.
Xinqi Liu1, Shaodong Dai, Yanan Zhu
1Howard Hughes Medical Institute, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA.
Immunity
|September 23, 2003
Summary
Activated T cell apoptosis involves Bcl-2 proteins like Bim and Bax/Bak. Structural studies reveal how Bim interacts with Bax, potentially activating it and driving T cell death.
Area of Science:
- Immunology
- Molecular Biology
- Structural Biology
Background:
- T cell apoptosis is crucial for immune response regulation.
- Bcl-2 family proteins, including Bim, Bax, and Bak, mediate this apoptosis.
- The precise mechanisms of Bim-Bax/Bak interaction and activation remain incompletely understood.
Purpose of the Study:
- To elucidate the structural basis of Bim interaction with Bax.
- To understand how Bim binding leads to Bax activation.
- To clarify the role of Bim and Bax/Bak in T cell apoptosis.
Main Methods:
- X-ray crystallography of mouse Bcl-x(L) bound to Bim.
- Structural homology modeling between Bcl-x(L) and Bax.
- Biochemical assays to test Bim/Bax interaction and Bax activation upon helix truncation.
Main Results:
- The crystal structure revealed Bim's unique fold, with a potentially exposed BH3 region.
- Structural homology suggested Bim binding to Bax requires displacement of Bax's penultimate alpha helix.
- Truncation of this helix facilitated Bim/Bax interaction and induced spontaneous Bax activation.
Conclusions:
- Bim's interaction with Bax involves the displacement of Bax's alpha helix.
- This interaction mechanism likely leads to Bax activation, promoting T cell apoptosis.
- Both Bim and Bax/Bak are essential components in the process of activated T cell death.