Cited by 1,476Cell death mechanisms and regulationProtein Structure and DynamicsCancer-related Molecular Pathways

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

Sattler, Michael, Liang, Heng, Nettesheim, David, Meadows, Robert P., Harlan, John E., Eberstadt, Matthias, Yoon, Ho Sup, Shuker, Suzanne B. +4 more·1997·Science

Abstract

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-x L 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 α helix that interacts with Bcl-x L 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-x L .

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Crossref · 10.1126/science.275.5302.983

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Authors
Sattler, M., Liang, H., Nettesheim, D., Meadows, R. P., Harlan, J. E., Eberstadt, M., Yoon, H. S., Shuker, S. B., Chang, B. S., Minn, A. J., Thompson, C. B., & Fesik, S. W.
Affiliations
  • Abbott (United States) (US)
  • Howard Hughes Medical Institute (US)
Venue
Science
Published
1997-02-14
Volume
275
Issue
5302
Pages
983-986
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2106799894
Cited by
1,476
References
13
Citations by year
2026: 18 · 2025: 22 · 2024: 16 · 2023: 34 · 2022: 29 · 2021: 32 · 2020: 32 · 2019: 34 · 2018: 38 · 2017: 42 · 2016: 41 · 2015: 51 · 2014: 57 · 2013: 69 · 2012: 60
FWCI
22.16
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • DR-NTU (Nanyang Technological University) (submittedVersion)
Funders
  • National Institutes of Health (5r37ca048023-14)
  • U.S. Public Health Service (P01 A135294)
  • National Cancer Institute (R37CA48023)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Keywords
Bcl-xL, Bak, Bcl-2 family proteins, apoptosis regulation, protein heterodimerization, amphipathic helix, hydrophobic interactions, electrostatic interactions
MeSH terms
Amino Acid Sequence, Membrane Proteins, Models, Molecular, Molecular Sequence Data, Magnetic Resonance Spectroscopy, Protein Conformation, Proto-Oncogene Proteins, Apoptosis, Sequence Deletion, Protein Structure, Secondary, Crystallography, X-Ray, Proto-Oncogene Proteins c-bcl-2, Dimerization, bcl-2 Homologous Antagonist-Killer Protein, bcl-X Protein

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