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Keywords {🔍}

bax, pubmed, bak, article, proteins, google, scholar, cas, cell, central, activation, bcl, bhonly, prosurvival, groove, apoptosis, binding, membrane, domain, biol, proapoptotic, mode, family, conformation, mitochondrial, death, figure, apoptotic, protein, activated, helices, oligomerization, structure, mitochondria, function, model, mom, peptide, nature, members, inhibition, chem, pore, residues, cells, activate, peptides, hydrophobic, change, dewson,

Topics {✒️}

nature portfolio permissions reprints privacy policy nature reviews advertising medical research nature 2005 nature 1996 nature 2008 nature social media normal development open questions research author information authors high-molecular weight oligomer bcl-xl/bim fragment complex c-terminal α6–α8 helices n-terminal α1–α5 helices intrinsic caspase-independent pathway author correspondence voltage-dependent-anion-channel2 bcl-xl-bak peptide complex parent full-length proteins core/latch dissociation exposes amino-acid sequence similarity full-length bax monomer full-length bax calculated anti-apoptotic context md e3 ligase ibrdc2 n-terminal 6a7 epitope full-length proapoptotic bak c-terminal α9 helix membrane-targeted death ligand cell damage-induced conformational �retro-translocation’ remains obscure bax channel-forming activity pro-apoptotic protein bak improves long-term function willis sn permissions α1/α2 loop displacement regulating protein–protein interactions groove interaction central opoku-nsiah ka operational infrastructure grants pro-survival proteins solid-state nmr investigation structural data supporting bak c-terminus mutant

Questions {❓}

• Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria?
• Are both proposed binding sites on Bax essential for its activation by BH3-only proteins?
• Cytosolic Bax: does it require binding proteins to keep its pro-apoptotic activity in check?
• Does Bax and Bak pore formation involve insertion of their α5/α6 helices as a membrane-spanning hairpin?
• Pharmacological manipulation of cell death: clinical applications in sight?
• What molecular features present in Bax and Bak but not in the prosurvival proteins allow conformation change, oligomerization and pore formation?
• What protein:protein interfaces allow Bax and Bak to form high molecular weight oligomeric pores?
• What’s Next?

Schema {🗺️}

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      headline:Building blocks of the apoptotic pore: how Bax and Bak are activated and oligomerize during apoptosis
      description:The central role of the Bcl-2 family in regulating apoptotic cell death was first identified in the 1980s. Since then, significant in-roads have been made in identifying the multiple members of this family, characterizing their form and function and understanding how their interactions determine whether a cell lives or dies. In this review we focus on the recent progress made in characterizing the proapoptotic Bcl-2 family members, Bax and Bak. This progress has resolved longstanding controversies, but has also challenged established theories in the apoptosis field. We will discuss different models of how these two proteins become activated and different ‘modes’ by which they are inhibited by other Bcl-2 family members. We will also discuss novel conformation changes leading to Bak and Bax oligomerization and speculate how these oligomers might permeabilize the mitochondrial outer membrane.
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