ArticleThe Journal of biological chemistry2011
Mutation to Bax beyond the BH3 domain disrupts interactions with pro-survival proteins and promotes apoptosis.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 120 citations in OpenAlex.
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- Targeted Penetrating Motif Engineering of BH3 Mimetic: Harnessing Non-Canonical Amino Acids for Coinhibition of MCL-1 and BCL-xL in Acute Myeloid Leukemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Deciphering molecular specificity in MCL-1/BAK interaction and its implications for designing potent MCL-1 inhibitors.Cell death and differentiation · 2025Article
- Structural basis of BAK sequestration by MCL-1 in apoptosis.Molecular cell · 2025Article
- Near telomere-to-telomere genome assemblies of Silkie Gallus gallus and Mallard Anas platyrhynchos restored the structure of chromosomes and "missing" genes in birds.Journal of animal science and biotechnology · 2025Article
- A novel inhibitory BAK antibody enables assessment of non-activated BAK in cancer cells.Cell death and differentiation · 2024Article
- Cyclic peptides discriminate BCL-2 and its clinical mutants from BCL-XNature communications · 2024Article
- Structural basis for proapoptotic activation of Bak by the noncanonical BH3-only protein Pxt1.PLoS biology · 2023Article
- Study of the Bcl-2 Interactome by BiFC Reveals Differences in the Activation Mechanism of Bax and Bak.Cells · 2023Article
- Crystal Structures of Epstein-Barr Virus Bcl-2 Homolog BHRF1 Bound to Bid and Puma BH3 Motif Peptides.Viruses · 2022Article
- The PI3K/AKT signaling pathway: How does it regulate development of Sertoli cells and spermatogenic cells?Histology and histopathology · 2022Review
- Nanomedicine Strategies for Management of Drug Resistance in Lung Cancer.International journal of molecular sciences · 2022Review
- Structural Details of BH3 Motifs and BH3-Mediated Interactions: an Updated Perspective.Frontiers in molecular biosciences · 2022Review
- Structural Investigation of Orf Virus Bcl-2 Homolog ORFV125 Interactions with BH3-Motifs from BH3-Only Proteins Puma and Hrk.Viruses · 2021Article
- Cell-penetrating Alphabody protein scaffolds for intracellular drug targeting.Science advances · 2021Article
- Poxviral Strategies to Overcome Host Cell Apoptosis.Pathogens (Basel, Switzerland) · 2020Review
- The structural basis of Bcl-2 mediated cell death regulation in hydra.The Biochemical journal · 2020Article
- AlphaSpace 2.0: Representing Concave Biomolecular Surfaces Using β-Clusters.Journal of chemical information and modeling · 2020Article
- Cooperation of Dnmt3a R878H with Nras G12D promotes leukemogenesis in knock-in mice: a pilot study.BMC cancer · 2019Article
- Docking-based approach for identification of mutations that disrupt binding between Bcl-2 and Bax proteins: Inducing apoptosis in cancer cells.Molecular genetics & genomic medicine · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pro-survival members of the Bcl-2 family of proteins restrain the pro-apoptotic activity of Bax, either directly through interactions with Bax or indirectly by sequestration of activator BH3-only proteins, or both. Mutations in Bax that promote apoptosis can provide insight into how Bax is regulated. Here, we describe crystal structures of the pro-survival proteins Mcl-1 and Bcl-x(L) in complex with a 34-mer peptide from Bax that encompasses its BH3 domain. These structures reveal canonical interactions between four signature hydrophobic amino acids from the BaxBH3 domain and the BH3-binding groove of the pro-survival proteins. In both structures, Met-74 from the Bax peptide engages with the BH3-binding groove in a fifth hydrophobic interaction. Various Bax Met-74 mutants disrupt interactions between Bax and all pro-survival proteins, but these Bax mutants retain pro-apoptotic activity. Bax/Bak-deficient mouse embryonic fibroblast cells reconstituted with several Bax Met-74 mutants are more sensitive to the BH3 mimetic compound ABT-737 as compared with cells expressing wild-type Bax. Furthermore, the cells expressing Bax Met-74 mutants are less viable in colony assays even in the absence of an external apoptotic stimulus. These results support a model in which direct restraint of Bax by pro-survival Bcl-2 proteins is a barrier to apoptosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.