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Science 14 February 1997:
Vol. 275. no. 5302, pp. 983 - 986
DOI: 10.1126/science.275.5302.983
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Reports

Structure of Bcl-xL-Bak Peptide Complex: Recognition Between Regulators of Apoptosis

Michael Sattler, Heng Liang, David Nettesheim, Robert P. Meadows, John E. Harlan, Matthias Eberstadt, Ho Sup Yoon, Suzanne B. Shuker, Brian S. Chang, Andy J. Minn, Craig B. Thompson, Stephen W. Fesik *

Heterodimerization between members of the Bcl-2 family of proteins is a key event in the regulation of programmed cell death. The molecular basis for heterodimer formation was investigated by determination of the solution structure of a complex between the survival protein Bcl-xL and the death-promoting region of the Bcl-2-related protein Bak. The structure and binding affinities of mutant Bak peptides indicate that the Bak peptide adopts an amphipathic alpha  helix that interacts with Bcl-xL through hydrophobic and electrostatic interactions. Mutations in full-length Bak that disrupt either type of interaction inhibit the ability of Bak to heterodimerize with Bcl-xL.

M. Sattler, H. Liang, D. Nettesheim, R. P. Meadows, J. E. Harlan, M. Eberstadt, H. S. Yoon, S. B. Shuker, S. W. Fesik, Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, IL 60064, USA.
B. S. Chang, A. J. Minn, C. B. Thompson, Howard Hughes Medical Institute and Departments of Medicine, Molecular Genetics, and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
*   To whom correspondence should be addressed.

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   Abstract »    Full Text »    PDF »
In vivo cooperation between Bcl-xL and the phosphoinositide 3-kinase-Akt signaling pathway for the protection of epidermal keratinocytes from apoptosis.
J. UMEDA, S. SANO, K. KOGAWA, N. MOTOYAMA, K. YOSHIKAWA, S. ITAMI, G. KONDOH, T. WATANABE, and J. TAKEDA (2003)
FASEB J 17, 610-620
   Abstract »    Full Text »    PDF »
Raf-1 and Bcl-2 Induce Distinct and Common Pathways That Contribute to Breast Cancer Drug Resistance.
J. M. Davis, P. M. Navolanic, C. R. Weinstein-Oppenheimer, L. S. Steelman, W. Hu, M. Konopleva, M. V. Blagosklonny, and J. A. McCubrey (2003)
Clin. Cancer Res. 9, 1161-1170
   Abstract »    Full Text »    PDF »
Characterization of the signal that directs Bcl-xL, but not Bcl-2, to the mitochondrial outer membrane.
T. Kaufmann, S. Schlipf, J. Sanz, K. Neubert, R. Stein, and C. Borner (2003)
J. Cell Biol. 160, 53-64
   Abstract »    Full Text »    PDF »
Advances in Biology and Therapy of Multiple Myeloma.
S. Barille-Nion, B. Barlogie, R. Bataille, P. L. Bergsagel, J. Epstein, R. G. Fenton, J. Jacobson, W. M. Kuehl, J. Shaughnessy, and G. Tricot (2003)
Hematology 2003, 248-278
   Abstract »    Full Text »    PDF »
Bcl-xL Complements Saccharomyces cerevisiae Genes That Facilitate the Switch from Glycolytic to Oxidative Metabolism.
M. G. Vander Heiden, J. S. Choy, D. J. VanderWeele, J. L. Brace, M. H. Harris, D. E. Bauer, B. Prange, S. J. Kron, C. B. Thompson, and C. M. Rudin (2002)
J. Biol. Chem. 277, 44870-44876
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Viral homologs of BCL-2: role of apoptosis in the regulation of virus infection.
A. Cuconati and E. White (2002)
Genes & Dev. 16, 2465-2478
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c-Myc Functionally Cooperates with Bax To Induce Apoptosis.
P. Juin, A. Hunt, T. Littlewood, B. Griffiths, L. B. Swigart, S. Korsmeyer, and G. Evan (2002)
Mol. Cell. Biol. 22, 6158-6169
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The Apoptotic Protein tBid Promotes Leakage by Altering Membrane Curvature.
R. F. Epand, J.-C. Martinou, M. Fornallaz-Mulhauser, D. W. Hughes, and R. M. Epand (2002)
J. Biol. Chem. 277, 32632-32639
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Effects of microinjection of synthetic Bcl-2 domain peptides on apoptosis of renal tubular epithelial cells.
E. Peherstorfer, B. Mayer, S. Boehm, A. Lukas, P. Hauser, G. Mayer, and R. Oberbauer (2002)
Am J Physiol Renal Physiol 283, F190-F196
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Siva-1 binds to and inhibits BCL-XL-mediated protection against UV radiation-induced apoptosis.
L. Xue, F. Chu, Y. Cheng, X. Sun, A. Borthakur, M. Ramarao, P. Pandey, M. Wu, S. F. Schlossman, and K. V. S. Prasad (2002)
PNAS 99, 6925-6930
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Identification and Characterization of Bim{gamma}, a Novel Proapoptotic BH3-only Splice Variant of Bim.
J.-W. Liu, D. Chandra, S.-H. Tang, D. Chopra, and D. G. Tang (2002)
Cancer Res. 62, 2976-2981
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BH3-only proteins -- evolutionarily conserved proapoptotic Bcl-2 family members essential for initiating programmed cell death.
P. Bouillet and A. Strasser (2002)
J. Cell Sci. 115, 1567-1574
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