Interaction with a membrane surface triggers a reversible conformational change in Bax normally associated with induction of apoptosis - PubMed (original) (raw)
. 2003 Dec 5;278(49):48935-41.
doi: 10.1074/jbc.M306289200. Epub 2003 Sep 30.
Affiliations
- PMID: 14522999
- DOI: 10.1074/jbc.M306289200
Free article
Interaction with a membrane surface triggers a reversible conformational change in Bax normally associated with induction of apoptosis
Jeremy A Yethon et al. J Biol Chem. 2003.
Free article
Abstract
The Bcl-2 family member Bax is an apoptosis-promoting protein that normally resides in an inactive state within the cytoplasm of healthy cells. Upon induction of apoptosis by diverse stimuli, Bax undergoes a conformational change and translocates to mitochondria, where it oligomerizes and forms pores that allow the release of cytochrome c and other cytotoxic factors. Protein-protein interactions between Bax and other Bcl-2 family members are strongly implicated in Bax activation, but a compelling case has recently been made for the involvement of lipids in this process as well. Here we report that purified Bax undergoes a reversible conformational change upon incubation with lipid vesicles in the absence of other proteins. This Bax-liposome interaction does not depend on a specific lipid composition. Changes in Bax conformation were observed by immunoprecipitation with the conformation-specific antibody 6A7, circular dichroism spectroscopy, and differential scanning calorimetry. Although liposomes induced Bax to become 6A7-reactive (a feature normally associated with the onset of apoptosis), the protein did not insert into membranes, become oligomeric, or form pores, clearly indicating that other triggers are required for Bax to achieve its final pro-apoptotic state. Indeed, the lipid-induced Bax conformational change is shown to be required for tBid-induced Bax oligomerization and pore formation, putting it upstream of tBid activity in this molecular pathway to Bax activation. These data demonstrate that Bax is sensitized to activation by transient interaction with lipid membrane surfaces and provide evidence that Bax activation proceeds in a stepwise fashion, with multiple triggers and potential levels of regulation.
Similar articles
- Distinct lipid effects on tBid and Bim activation of membrane permeabilization by pro-apoptotic Bax.
Shamas-Din A, Bindner S, Chi X, Leber B, Andrews DW, Fradin C. Shamas-Din A, et al. Biochem J. 2015 May 1;467(3):495-505. doi: 10.1042/BJ20141291. Biochem J. 2015. PMID: 25714678 - Bid induces cytochrome c-impermeable Bax channels in liposomes.
Roucou X, Rostovtseva T, Montessuit S, Martinou JC, Antonsson B. Roucou X, et al. Biochem J. 2002 May 1;363(Pt 3):547-52. doi: 10.1042/0264-6021:3630547. Biochem J. 2002. PMID: 11964155 Free PMC article. - Bax oligomerization in mitochondrial membranes requires tBid (caspase-8-cleaved Bid) and a mitochondrial protein.
Roucou X, Montessuit S, Antonsson B, Martinou JC. Roucou X, et al. Biochem J. 2002 Dec 15;368(Pt 3):915-21. doi: 10.1042/BJ20020972. Biochem J. 2002. PMID: 12193163 Free PMC article. - Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c.
Korsmeyer SJ, Wei MC, Saito M, Weiler S, Oh KJ, Schlesinger PH. Korsmeyer SJ, et al. Cell Death Differ. 2000 Dec;7(12):1166-73. doi: 10.1038/sj.cdd.4400783. Cell Death Differ. 2000. PMID: 11175253 Review. - Bax. The pro-apoptotic Bcl-2 family member, Bax.
Brady HJ, Gil-Gómez G. Brady HJ, et al. Int J Biochem Cell Biol. 1998 Jun;30(6):647-50. doi: 10.1016/s1357-2725(98)00006-5. Int J Biochem Cell Biol. 1998. PMID: 9695020 Review.
Cited by
- The membrane insertion of the pro-apoptotic protein Bax is a Tom22-dependent multi-step process: a study in nanodiscs.
Rouchidane Eyitayo A, Daury L, Priault M, Manon S. Rouchidane Eyitayo A, et al. Cell Death Discov. 2024 Jul 23;10(1):335. doi: 10.1038/s41420-024-02108-x. Cell Death Discov. 2024. PMID: 39043635 Free PMC article. - Bcl-xL Is Spontaneously Inserted into Preassembled Nanodiscs and Stimulates Bax Insertion in a Cell-Free Protein Synthesis System.
Rouchidane Eyitayo A, Boudier-Lemosquet A, Chaignepain S, Priault M, Manon S. Rouchidane Eyitayo A, et al. Biomolecules. 2023 May 23;13(6):876. doi: 10.3390/biom13060876. Biomolecules. 2023. PMID: 37371456 Free PMC article. - BCL-2-family protein tBID can act as a BAX-like effector of apoptosis.
Flores-Romero H, Hohorst L, John M, Albert MC, King LE, Beckmann L, Szabo T, Hertlein V, Luo X, Villunger A, Frenzel LP, Kashkar H, Garcia-Saez AJ. Flores-Romero H, et al. EMBO J. 2022 Dec 17;41(2):e108690. doi: 10.15252/embj.2021108690. Epub 2021 Dec 21. EMBO J. 2022. PMID: 34931711 Free PMC article. - High-resolution analysis of the conformational transition of pro-apoptotic Bak at the lipid membrane.
Sperl LE, Rührnößl F, Schiller A, Haslbeck M, Hagn F. Sperl LE, et al. EMBO J. 2021 Oct 18;40(20):e107159. doi: 10.15252/embj.2020107159. Epub 2021 Sep 15. EMBO J. 2021. PMID: 34523144 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials