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Proc Natl Acad Sci U S A. 2017 Jan 10;114(2):310-315. doi: 10.1073/pnas.1612322114. Epub 2016 Dec 27.

Bax transmembrane domain interacts with prosurvival Bcl-2 proteins in biological membranes.

Author information

1
Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, E-46012 Valencia, Spain.
2
Institute for Biochemistry and Molecular Biology, University of Freiburg, 79104 Freiburg, Germany.
3
Departament de Bioquímica i Biologia Molecular, Estructura de Recerca Interdisciplinar en Biotecnología i Biomedicina, Universitat de València, 46100 Burjassot, Spain.
4
Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
5
Department of Biochemistry/Biotechnology, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany.
6
Instituto de Biomedicina de Valencia, Instituto de Biomedicina de Valencia-Consejo Superior de Investigaciones Científicas, 46010 Valencia, Spain.
7
Departament de Bioquímica i Biologia Molecular, Estructura de Recerca Interdisciplinar en Biotecnología i Biomedicina, Universitat de València, 46100 Burjassot, Spain; morzaez@cipf.es Ismael.Mingarro@uv.es frank.edlich@biochemie.uni-freiburg.de.
8
Institute for Biochemistry and Molecular Biology, University of Freiburg, 79104 Freiburg, Germany; morzaez@cipf.es Ismael.Mingarro@uv.es frank.edlich@biochemie.uni-freiburg.de.
9
BIOSS, Centre for Biological Signaling Studies, University of Freiburg, 79104 Freiburg, Germany.
10
Laboratory of Peptide and Protein Chemistry, Centro de Investigación Príncipe Felipe, E-46012 Valencia, Spain; morzaez@cipf.es Ismael.Mingarro@uv.es frank.edlich@biochemie.uni-freiburg.de.

Abstract

The Bcl-2 (B-cell lymphoma 2) protein Bax (Bcl-2 associated X, apoptosis regulator) can commit cells to apoptosis via outer mitochondrial membrane permeabilization. Bax activity is controlled in healthy cells by prosurvival Bcl-2 proteins. C-terminal Bax transmembrane domain interactions were implicated recently in Bax pore formation. Here, we show that the isolated transmembrane domains of Bax, Bcl-xL (B-cell lymphoma-extra large), and Bcl-2 can mediate interactions between Bax and prosurvival proteins inside the membrane in the absence of apoptotic stimuli. Bcl-2 protein transmembrane domains specifically homooligomerize and heterooligomerize in bacterial and mitochondrial membranes. Their interactions participate in the regulation of Bcl-2 proteins, thus modulating apoptotic activity. Our results suggest that interactions between the transmembrane domains of Bax and antiapoptotic Bcl-2 proteins represent a previously unappreciated level of apoptosis regulation.

KEYWORDS:

Bcl-2; apoptosis; mitochondria; oligomerization; transmembrane

PMID:
28028215
PMCID:
PMC5240701
DOI:
10.1073/pnas.1612322114
[Indexed for MEDLINE]
Free PMC Article

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