Structure of detergent-activated BAK dimers derived from the inert monomer.

Amino Acid Sequence Animals Detergents / chemistry Liposomes Mice, Inbred C57BL Mice, Knockout Models, Molecular Protein Multimerization Protein Structure, Secondary bcl-2 Homologous Antagonist-Killer Protein / chemistry
Apoptosis BAK BAK activation BCL-2 family proteins BH3-in-groove core dimers Detergent mediated dimerization X-ray crystallography cytochrome c release membrane rupture

Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
20 05 2021
Historique:
received: 04 09 2020
revised: 11 01 2021
accepted: 09 03 2021
pubmed: 2 4 2021
medline: 17 6 2021
entrez: 1 4 2021
Statut: ppublish

Résumé

A body of data supports the existence of core (α2-α5) dimers of BAK and BAX in the oligomeric, membrane-perturbing conformation of these essential apoptotic effector molecules. Molecular structures for these dimers have only been captured for truncated constructs encompassing the core domain alone. Here, we report a crystal structure of BAK α2-α8 dimers (i.e., minus its flexible N-terminal helix and membrane-anchoring C-terminal segment) that has been obtained through the activation of monomeric BAK with the detergent C12E8. Core dimers are evident, linked through the crystal by contacts via latch (α6-α8) domains. This crystal structure shows activated BAK dimers with the extended latch domain present. Our data provide direct evidence for the conformational change converting BAK from inert monomer to the functional dimer that destroys mitochondrial integrity. This dimer is the smallest functional unit for recombinant BAK or BAX described so far.

Identifiants

DOI: 10.1016/j.molcel.2021.03.014 PMID: 33794146
pubmed: 33794146
pii: S1097-2765(21)00182-9
doi: 10.1016/j.molcel.2021.03.014
pii:
doi:

Substances chimiques

Detergents 0
Liposomes 0
bcl-2 Homologous Antagonist-Killer Protein 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2123-2134.e5

Informations de copyright

Copyright © 2021 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Richard W Birkinshaw (RW)

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia. Electronic address: birkinshaw.r@wehi.edu.au.

Sweta Iyer (S)

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.

Daisy Lio (D)

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.

Cindy S Luo (CS)

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.

Jason M Brouwer (JM)

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.

Michelle S Miller (MS)

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.

Adeline Y Robin (AY)

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.

Rachel T Uren (RT)

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.

Grant Dewson (G)

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.

Ruth M Kluck (RM)

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.

Peter M Colman (PM)

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia.

Peter E Czabotar (PE)

The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Melbourne, VIC 3052, Australia; Department of Medical Biology, University of Melbourne, Melbourne, VIC 3010, Australia. Electronic address: czabotar@wehi.edu.au.

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Classifications MeSH

questionsmedicales.fr › Sciences de l'information › Sources d'information › Services d'information › Documentation › Données de séquences moléculaires › Séquence d'acides aminés › Structure of detergent-activated BAK dimers...
questionsmedicales.fr › Eucaryotes › Animaux › Structure of detergent-activated BAK dimers...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits domestiques › Détergents › Structure of detergent-activated BAK dimers...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Matériaux biomimétiques › Membrane artificielle › Liposomes › Structure of detergent-activated BAK dimers...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Structure of detergent-activated BAK dimers...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › Structure of detergent-activated BAK dimers...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles moléculaires › Structure of detergent-activated BAK dimers...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Multimérisation de protéines › Structure of detergent-activated BAK dimers...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes biochimiques › Conformation moléculaire › Conformation des protéines › Structure secondaire des protéines › Structure of detergent-activated BAK dimers...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines régulatrices de l'apoptose › Protéine Bak › Structure of detergent-activated BAK dimers...