ArticleThe Journal of biological chemistry2014
After embedding in membranes antiapoptotic Bcl-XL protein binds both Bcl-2 homology region 3 and helix 1 of proapoptotic Bax protein to inhibit apoptotic mitochondrial permeabilization.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 76 citations in OpenAlex.
- Multifaceted Roles of Bcl-2 Family Proteins: Regulatory Roles in Apoptosis, Physiological Functions, and Therapeutic Potential.Current medical science · 2025Review
- Allosteric regulation of BH3-in-groove interactions by tail anchors of BCL-xL complexes limits BH3 mimetic antagonism.Nature communications · 2025Article
- Bax- Bcl-xL interaction dynamics during the progression of cell cycle and cell death using FLIM-FRET.Cell stress · 2025Review
- The C-terminal sequences of Bcl-2 family proteins mediate interactions that regulate cell death.The Biochemical journal · 2024Review
- Apoptosis in glaucoma: A new direction for the treatment of glaucoma (Review).Molecular medicine reports · 2024Review
- Effect of Celastrus Orbiculatus Extract on proliferation and apoptosis of human Burkitt lymphoma cells.Frontiers in pharmacology · 2024Article
- Study of the Bcl-2 Interactome by BiFC Reveals Differences in the Activation Mechanism of Bax and Bak.Cells · 2023Article
- Apoptotic priming is defined by the dynamic exchange of Bcl-2 proteins between mitochondria and cytosol.Cell death and differentiation · 2022Article
- Roles of calpain in the apoptosis of Eimeria tenella host cells at the middle and late developmental stages.Parasitology research · 2022Article
- Structural insights into apoptotic regulation of human Bfk as a novel Bcl-2 family member.Computational and structural biotechnology journal · 2022Article
- Regulated cell death: discovery, features and implications for neurodegenerative diseases.Cell communication and signaling : CCS · 2021Review
- Effects of acute hypoxia and reoxygenation on oxygen sensors, respiratory metabolism, oxidative stress, and apoptosis in hybrid yellow catfish "Huangyou-1".Fish physiology and biochemistry · 2021Article
- Effects of Cardiolipin on the Conformational Dynamics of Membrane-Anchored Bcl-xL.International journal of molecular sciences · 2021Article
- Neutron reflectometry and NMR spectroscopy of full-length Bcl-2 protein reveal its membrane localization and conformation.Communications biology · 2021Article
- Synergistic anti-tumor effect of anti-PD-L1 antibody cationic microbubbles for delivery of the miR-34a gene combined with ultrasound on cervical carcinoma.American journal of translational research · 2021Article
- Cysteine-based crosslinking approach for characterization of oligomeric pore-forming proteins in the mitochondrial membranes.Methods in enzymology · 2021Article
- 7-Chloroquinoline-1,2,3-triazoyl carboxamides induce cell cycle arrest and apoptosis in human bladder carcinoma cells.Investigational new drugs · 2020Article
- Stoichiometry and regulation network of Bcl-2 family complexes quantified by live-cell FRET assay.Cellular and molecular life sciences : CMLS · 2020Article
- Mitochondria: A Galaxy in the Hematopoietic and Leukemic Stem Cell Universe.International journal of molecular sciences · 2020Review
- Bcl-2-Protein Family as Modulators of IPCold Spring Harbor perspectives in biology · 2020Review
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 4 countries.
Funding
Abstract
Bcl-XL binds to Bax, inhibiting Bax oligomerization required for mitochondrial outer membrane permeabilization (MOMP) during apoptosis. How Bcl-XL binds to Bax in the membrane is not known. Here, we investigated the structural organization of Bcl-XL·Bax complexes formed in the MOM, including the binding interface and membrane topology, using site-specific cross-linking, compartment-specific labeling, and computational modeling. We found that one heterodimer interface is formed by a specific interaction between the Bcl-2 homology 1-3 (BH1-3) groove of Bcl-XL and the BH3 helix of Bax, as defined previously by the crystal structure of a truncated Bcl-XL protein and a Bax BH3 peptide (Protein Data Bank entry 3PL7). We also discovered a novel interface in the heterodimer formed by equivalent interactions between the helix 1 regions of Bcl-XL and Bax when their helical axes are oriented either in parallel or antiparallel. The two interfaces are located on the cytosolic side of the MOM, whereas helix 9 of Bcl-XL is embedded in the membrane together with helices 5, 6, and 9 of Bax. Formation of the helix 1·helix 1 interface partially depends on the formation of the groove·BH3 interface because point mutations in the latter interface and the addition of ABT-737, a groove-binding BH3 mimetic, blocked the formation of both interfaces. The mutations and ABT-737 also prevented Bcl-XL from inhibiting Bax oligomerization and subsequent MOMP, suggesting that the structural organization in which interactions at both interfaces contribute to the overall stability and functionality of the complex represents antiapoptotic Bcl-XL·Bax complexes in the MOM.
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