Crystal Structure of the Bcl-XL-Beclin 1 Peptide Complex
Bcl-2 family proteins are key regulators of apoptosis and have recently been shown to modulate autophagy. The tumor suppressor Beclin 1 has been proposed to coordinate both apoptosis and autophagy through direct interaction with anti-apoptotic family members Bcl-2 and/or Bcl-X{sub L}. However, the molecular basis for this interaction remains enigmatic. Here we report that Beclin 1 contains a conserved BH3 domain, which is both necessary and sufficient for its interaction with Bcl-X{sub L}. We also report the crystal structure of a Beclin BH3 peptide in complex with Bcl-X{sub L} at 2.5{angstrom} resolution. Reminiscent of previously determined Bcl-X{sub L}-BH3 structures, the amphipathic BH3 helix of Beclin 1 bound to a conserved hydrophobic groove of Bcl-X{sub L}. These results define Beclin 1 as a novel BH3-only protein, implying that Beclin 1 may have a direct role in initiating apoptotic signaling. We propose that this putative apoptotic function may be linked to the ability of Beclin 1 to suppress tumor formation in mammals.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 929991
- Report Number(s):
- BNL-80600-2008-JA; JBCHA3; TRN: US200822%%1146
- Journal Information:
- Journal of Biological Chemistry, Vol. 282, Issue 17; ISSN 0021-9258
- Country of Publication:
- United States
- Language:
- English
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