Abstract
The Bcl-2 family of proteins have been shown to play an essential role in the regulation of programmed cell death. Within the cell, Bcl-2 and related proteins are expressed on the outer membranes of mitochondria, the nucleus, and the endoplasmic reticulum. The significance of this membrane-associated distribution is unclear because the molecular mechanism(s) by which Bcl-2 proteins modulate apoptosis in unknown. To gain further insight into these issues, the crystal and solution structure of a Bct-2 family member, Bcl-xL has been determined. The structure consists of two central, primarily hydrophobic a-helices which are surrounded by amphipathetic helices. A flexible 60 residue loop connects helices 1 and 2 and was found to be nonessential for anti-apoptotic activity. Portions of three functionally important Bcl-2 homology regions (BH1, BH2, and BH3) form an elongated hydrophobic cleft which may represent the binding site for other Bcl-2 family members that promote apoptosis. The three-layered arrangement of the cx-helicies is reminiscent of the membrane translocation domain of bacterial toxins, in particular dtptheria toxin and the colicins. This structural similarity may provide a clue to the mechanism of action of the Bcl-2 family of proteins.
| Original language | English |
|---|---|
| Pages (from-to) | A1087 |
| Journal | FASEB Journal |
| Volume | 10 |
| Issue number | 6 |
| State | Published - 1996 |
| Externally published | Yes |