Dynamic interaction of cBid with detergents, liposomes and mitochondria.

The BH3-only protein Bid plays a key role in the induction of mitochondrial apoptosis, but its mechanism of action is still not completely understood. Here we studied the two main activation events of Bid: Caspase-8 cleavage and interaction with the membrane bilayer. We found a striking reversible b...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Stephanie Bleicken, Ana J García-Sáez, Elena Conte, Enrica Bordignon
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/92d5f3e0136b4761b23ae1f6a761cb6c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:92d5f3e0136b4761b23ae1f6a761cb6c
record_format	dspace
spelling	oai:doaj.org-article:92d5f3e0136b4761b23ae1f6a761cb6c2021-11-18T07:21:13ZDynamic interaction of cBid with detergents, liposomes and mitochondria.1932-620310.1371/journal.pone.0035910https://doaj.org/article/92d5f3e0136b4761b23ae1f6a761cb6c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22540011/?tool=EBIhttps://doaj.org/toc/1932-6203The BH3-only protein Bid plays a key role in the induction of mitochondrial apoptosis, but its mechanism of action is still not completely understood. Here we studied the two main activation events of Bid: Caspase-8 cleavage and interaction with the membrane bilayer. We found a striking reversible behaviour of the dissociation-association events between the Bid fragments p15 and p7. Caspase-8 cleavage does not induce per se separation of the two Bid fragments, which remain in a stable complex resembling the full length Bid. Detergents trigger a complete dissociation, which can be fully reversed by detergent removal in a range of protein concentrations from 100 µM down to 500 nM. Incubation of cBid with cardiolipin-containing liposomes leads to partial dissociation of the complex. Only p15 (tBid) fragments are found at the membrane, while p7 shows no tendency to interact with the bilayer, but complete removal of p7 strongly increases the propensity of tBid to become membrane-associated. Despite the striking structural similarities of inactive Bid and Bax, Bid does not form oligomers and reacts differently in the presence of detergents and membranes, highlighting clear differences in the modes of action of the two proteins. The partial dissociation of cBid triggered by the membrane is suggested to depend on the strong and specific interaction between p15 and p7. The reversible disassembly and re-assembly of the cBid molecules at the membrane was as well proven by EPR using spin labeled cBid in the presence of isolated mitochondria. The observed dynamic dissociation of the two Bid fragments could allow the assistance to the pore-forming Bax to occur repeatedly and may explain the proposed "hit-and-run" mode of action of Bid at the bilayer.Stephanie BleickenAna J García-SáezElena ConteEnrica BordignonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35910 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stephanie Bleicken Ana J García-Sáez Elena Conte Enrica Bordignon Dynamic interaction of cBid with detergents, liposomes and mitochondria.
description	The BH3-only protein Bid plays a key role in the induction of mitochondrial apoptosis, but its mechanism of action is still not completely understood. Here we studied the two main activation events of Bid: Caspase-8 cleavage and interaction with the membrane bilayer. We found a striking reversible behaviour of the dissociation-association events between the Bid fragments p15 and p7. Caspase-8 cleavage does not induce per se separation of the two Bid fragments, which remain in a stable complex resembling the full length Bid. Detergents trigger a complete dissociation, which can be fully reversed by detergent removal in a range of protein concentrations from 100 µM down to 500 nM. Incubation of cBid with cardiolipin-containing liposomes leads to partial dissociation of the complex. Only p15 (tBid) fragments are found at the membrane, while p7 shows no tendency to interact with the bilayer, but complete removal of p7 strongly increases the propensity of tBid to become membrane-associated. Despite the striking structural similarities of inactive Bid and Bax, Bid does not form oligomers and reacts differently in the presence of detergents and membranes, highlighting clear differences in the modes of action of the two proteins. The partial dissociation of cBid triggered by the membrane is suggested to depend on the strong and specific interaction between p15 and p7. The reversible disassembly and re-assembly of the cBid molecules at the membrane was as well proven by EPR using spin labeled cBid in the presence of isolated mitochondria. The observed dynamic dissociation of the two Bid fragments could allow the assistance to the pore-forming Bax to occur repeatedly and may explain the proposed "hit-and-run" mode of action of Bid at the bilayer.
format	article
author	Stephanie Bleicken Ana J García-Sáez Elena Conte Enrica Bordignon
author_facet	Stephanie Bleicken Ana J García-Sáez Elena Conte Enrica Bordignon
author_sort	Stephanie Bleicken
title	Dynamic interaction of cBid with detergents, liposomes and mitochondria.
title_short	Dynamic interaction of cBid with detergents, liposomes and mitochondria.
title_full	Dynamic interaction of cBid with detergents, liposomes and mitochondria.
title_fullStr	Dynamic interaction of cBid with detergents, liposomes and mitochondria.
title_full_unstemmed	Dynamic interaction of cBid with detergents, liposomes and mitochondria.
title_sort	dynamic interaction of cbid with detergents, liposomes and mitochondria.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/92d5f3e0136b4761b23ae1f6a761cb6c
work_keys_str_mv	AT stephaniebleicken dynamicinteractionofcbidwithdetergentsliposomesandmitochondria AT anajgarciasaez dynamicinteractionofcbidwithdetergentsliposomesandmitochondria AT elenaconte dynamicinteractionofcbidwithdetergentsliposomesandmitochondria AT enricabordignon dynamicinteractionofcbidwithdetergentsliposomesandmitochondria
_version_	1718423612556312576

Dynamic interaction of cBid with detergents, liposomes and mitochondria.

Ejemplares similares