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

Muchmore SW, Sattler M, Liang H, Meadows RP, Harlan JE, Yoon HS, Nettesheim D, Chang BS, Thompson CB, Wong SL, Ng SL, Fesik SW
Nature. 1996 381 (6580): 335-41

PMID: 8692274 · DOI:10.1038/381335a0

THE Bcl-2 family of proteins regulate programmed cell death by an unknown mechanism. 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 alpha-helices, which are surrounded by amphipathic helices. A 60-residue loop connecting helices alpha1 and alpha2 was found to be flexible and non-essential for anti-apoptotic activity. The three functionally important Bcl-2 homology regions (BH1, BH2 and BH3) 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 alpha-helices in Bcl-xL is reminiscent of the membrane translocation domain of bacterial toxins, in particular diphtheria toxin and the colicins. The structural similarity may provide a clue to the mechanism of action of the Bcl-2 family of proteins.

MeSH Terms (13)

Amino Acid Sequence Apoptosis bcl-X Protein Crystallography, X-Ray Escherichia coli Humans Magnetic Resonance Spectroscopy Molecular Sequence Data Protein Conformation Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Recombinant Proteins Sequence Homology, Amino Acid

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