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Scientific article
English

Topology of active, membrane-embedded Bax in the context of a toroidal pore

Published inCell death and differentiation, vol. 25, no. 10, p. 1717-1731
Publication date2018-09-05
First online date2018-09-05
Abstract

Bax is a Bcl-2 protein critical for apoptosis induction. In healthy cells, Bax is mostly a monomeric, cytosolic protein, while upon apoptosis initiation it inserts into the outer mitochondrial membrane, oligomerizes, and forms pores that release proapoptotic factors like Cytochrome c into the cytosol. The structures of active Bax and its homolog Bak are only partially understood and the topology of the proteins with respect to the membrane bilayer is controversially described in the literature. Here, we systematically review and examine the protein–membrane, protein–water, and protein–protein contacts of the nine helices of active Bax and Bak, and add a new set of topology data obtained by fluorescence and EPR methods. We conclude based on the consistent part of the datasets that the core/dimerization domain of Bax (Bak) is water exposed with only helices 4 and 5 in membrane contact, whereas the piercing/latch domain is in peripheral membrane contact, with helix 9 being transmembrane. Among the available structural models, those considering the dimerization/core domain at the rim of a toroidal pore are the most plausible to describe the active state of the proteins, although the structural flexibility of the piercing/latch domain does not allow unambiguous discrimination between the existing models.

eng
Affiliation Not a UNIGE publication
Funding
  • Deutsche Forschungsgemeinschaft - [SPP1601]
  • European Research Council - [309966]
Citation (ISO format)
BLEICKEN, Stephanie et al. Topology of active, membrane-embedded Bax in the context of a toroidal pore. In: Cell death and differentiation, 2018, vol. 25, n° 10, p. 1717–1731. doi: 10.1038/s41418-018-0184-6
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ISSN of the journal1350-9047
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