Structure of Bcl-x L -Bak Peptide Complex: Recognition Between Regulators of Apoptosis
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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Mcl-1 is a crucial anti-apoptotic member of Bcl-2 family that contributes significantly to development of various human cancers.
“Myeloid cell leukemia-1 (Mcl-1) is a crucial anti-apoptotic member of the Bcl-2 protein family that contributes significantly to the development of various human cancers.”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [225]
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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)
- ORCID
- 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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