2P1L

Structure of the Bcl-XL:Beclin 1 complex

Summary for 2P1L

• Entry DOI: 10.2210/pdb2p1l/pdb
• Descriptor: Apoptosis regulator Bcl-X, Beclin 1 (3 entities in total)
• Functional Keywords: apoptosis; autophagy; beclin; bh3 domain; bcl, apoptosis
• Biological source: Homo sapiens (human); More
• Cellular location: Isoform Bcl-X(L): Mitochondrion inner membrane : Q07817; Cytoplasm . Beclin-1-C 35 kDa: Mitochondrion . Beclin-1-C 37 kDa: Mitochondrion : Q14457
• Total number of polymer chains: 8
• Total formula weight: 83553.02

Authors

Jeffrey, P.D.,Shi, Y.,Oberstein, A.L. (deposition date: 2007-03-05, release date: 2007-03-13, Last modification date: 2024-02-21)

Primary citation

Oberstein, A.,Jeffrey, P.D.,Shi, Y.
Crystal structure of the Bcl-XL-Beclin 1 peptide complex: Beclin 1 is a novel BH3-only protein
J.Biol.Chem., 282:13123-13132, 2007

PubMed Abstract: 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(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(L). We also report the crystal structure of a Beclin BH3 peptide in complex with Bcl-X(L) at 2.5A resolution. Reminiscent of previously determined Bcl-X(L)-BH3 structures, the amphipathic BH3 helix of Beclin 1 bound to a conserved hydrophobic groove of Bcl-X(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.

PubMed: 17337444
DOI: 10.1074/jbc.M700492200

Experimental method

X-RAY DIFFRACTION (2.5 Å)