ArticleThe EMBO journal2021
Dynamic reconfiguration of pro-apoptotic BAK on membranes.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed.
- Direct binding of the C-terminal sequences of Bim and Bak contributes to efficient Bak activation.Cell death and differentiation · 2026Article
- Hydroxysafflor yellow A attenuates sepsis-induced intestinal barrier dysfunction by modulating Bcl-2/SOD2-mediated mitochondrial apoptosis.Frontiers in pharmacology · 2026Article
- Article
- The BCL2 family: from apoptosis mechanisms to new advances in targeted therapy.Signal transduction and targeted therapy · 2025Review
- Inhibition of BAK-mediated apoptosis by the BH3-only protein BNIP5.Cell death and differentiation · 2025Article
- The C-terminal sequences of Bcl-2 family proteins mediate interactions that regulate cell death.The Biochemical journal · 2024Review
- Parkin-mediated ubiquitination inhibits BAK apoptotic activity by blocking its canonical hydrophobic groove.Communications biology · 2023Article
- Mechanisms of BCL-2 family proteins in mitochondrial apoptosis.Nature reviews. Molecular cell biology · 2023Review
- Pore-forming proteins as drivers of membrane permeabilization in cell death pathways.Nature reviews. Molecular cell biology · 2023Review
- Peptides from human BNIP5 and PXT1 and non-native binders of pro-apoptotic BAK can directly activate or inhibit BAK-mediated membrane permeabilization.Structure (London, England : 1993) · 2023Article
- Visualization of BOK pores independent of BAX and BAK reveals a similar mechanism with differing regulation.Cell death and differentiation · 2023Article
- A BAK subdomain that binds mitochondrial lipids selectively and releases cytochrome C.Cell death and differentiation · 2023Article
- Apoptotic mitochondrial poration by a growing list of pore-forming BCL-2 family proteins.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- Small molecule SJ572946 activates BAK to initiate apoptosis.iScience · 2022Article
- Protein-protein and protein-lipid interactions of pore-forming BCL-2 family proteins in apoptosis initiation.Biochemical Society transactions · 2022Review
- Therapeutic approaches targeting CD95L/CD95 signaling in cancer and autoimmune diseases.Cell death & disease · 2022Review
- Bcl-2 Family Members and the Mitochondrial Import Machineries: The Roads to Death.Biomolecules · 2022Review
- Structural basis of BAK activation in mitochondrial apoptosis initiation.Nature communications · 2022Article
- Yeast as a tool to decipher the molecular mechanisms underlying the functions of Bcl-2 family.Exploration of targeted anti-tumor therapy · 2022Review
- A killer metamorphosis: catching BAK in action at the membrane.The EMBO journal · 2021Article
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BAK and BAX, the effectors of intrinsic apoptosis, each undergo major reconfiguration to an activated conformer that self-associates to damage mitochondria and cause cell death. However, the dynamic structural mechanisms of this reconfiguration in the presence of a membrane have yet to be fully elucidated. To explore the metamorphosis of membrane-bound BAK, we employed hydrogen-deuterium exchange mass spectrometry (HDX-MS). The HDX-MS profile of BAK on liposomes comprising mitochondrial lipids was consistent with known solution structures of inactive BAK. Following activation, HDX-MS resolved major reconfigurations in BAK. Mutagenesis guided by our HDX-MS profiling revealed that the BCL-2 homology (BH) 4 domain maintains the inactive conformation of BAK, and disrupting this domain is sufficient for constitutive BAK activation. Moreover, the entire N-terminal region preceding the BAK oligomerisation domains became disordered post-activation and remained disordered in the activated oligomer. Removal of the disordered N-terminus did not impair, but rather slightly potentiated, BAK-mediated membrane permeabilisation of liposomes and mitochondria. Together, our HDX-MS analyses reveal new insights into the dynamic nature of BAK activation on a membrane, which may provide new opportunities for therapeutic targeting.
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Registered trials
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.