X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death

• Main Authors: Yoon, Ho Sup, Sattler, Michael, Muchmore, Steven W., Liang, Heng, Meadows, Robert P., Harlan, John E., Nettesheim, David G., Chang, Brian S., Thompson, Craig B., Wong, Sui-Lam, Ng, Shi-Chung, Fesik, Stephen W.
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2012
• Subjects: DRNTU::Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/95496; http://hdl.handle.net/10220/8302
• Institution: Nanyang Technological University

THE Bcl-2 family of proteins regulate programmed cell death by an unknown mechanism1. Here we describe the crystal and solution structures of a Bcl-2 family member, Bcl-xL (ref. 2). The structures consist of two central, primarily hydrophobic α-helices, which are surrounded by amphipathic helices. A 60-residue loop connecting helices αl and α2 was found to be flexible and non-essential for anti-apoptotic activity. The three functionally important Bcl-2 homology regions (BH1, BH2 and BH3)3–5 are in close spatial proximity and form an elongated hydrophobic cleft that may represent the binding site for other Bcl-2 family members. The arrangement of the α-helices in Bcl-xL is reminiscent of the membrane translocation domain of bacterial toxins, in particular diphtheria toxin and the colicins6. The structural similarity may provide a clue to the mechanism of action of the Bcl-2 family of proteins.