ArticleThe EMBO journal2021
High-resolution analysis of the conformational transition of pro-apoptotic Bak at the lipid membrane.
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 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Nucleotide-dependent switching and RIPb effector recognition of the barley susceptibility factor RACB.Communications biology · 2026Article
- Structural basis of apoptosis induction by the mitochondrial voltage-dependent anion channel.Nature communications · 2025Article
- The BCL-2 protein family: from discovery to drug development.Cell death and differentiation · 2025Review
- 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
- Eltrombopag directly activates BAK and induces apoptosis.Cell death & disease · 2023Article
- 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
- 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
- Detergent-Free Isolation of Membrane Proteins and Strategies to Study Them in a Near-Native Membrane Environment.Biomolecules · 2022Review
- 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
- Structural basis of BAK activation in mitochondrial apoptosis initiation.Nature communications · 2022Article
- A killer metamorphosis: catching BAK in action at the membrane.The EMBO journal · 2021Article
- High-resolution analysis of the conformational transition of pro-apoptotic Bak at the lipid membrane.The EMBO journal · 2021Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Permeabilization of the outer mitochondrial membrane by pore-forming Bcl2 proteins is a crucial step for the induction of apoptosis. Despite a large set of data suggesting global conformational changes within pro-apoptotic Bak during pore formation, high-resolution structural details in a membrane environment remain sparse. Here, we used NMR and HDX-MS (Hydrogen deuterium exchange mass spectrometry) in lipid nanodiscs to gain important high-resolution structural insights into the conformational changes of Bak at the membrane that are dependent on a direct activation by BH3-only proteins. Furthermore, we determined the first high-resolution structure of the Bak transmembrane helix. Upon activation, α-helix 1 in the soluble domain of Bak dissociates from the protein and adopts an unfolded and dynamic potentially membrane-bound state. In line with this finding, comparative protein folding experiments with Bak and anti-apoptotic BclxL suggest that α-helix 1 in Bak is a metastable structural element contributing to its pro-apoptotic features. Consequently, mutagenesis experiments aimed at stabilizing α-helix 1 yielded Bak variants with delayed pore-forming activity. These insights will contribute to a better mechanistic understanding of Bak-mediated membrane permeabilization.
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