The mechanism of toxicity in HET-S/HET-s prion incompatibility.

The HET-s protein from the filamentous fungus Podospora anserina is a prion involved in a cell death reaction termed heterokaryon incompatibility. This reaction is observed at the point of contact between two genetically distinct strains when one harbors a HET-s prion (in the form of amyloid aggrega...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Carolin Seuring, Jason Greenwald, Christian Wasmer, Roger Wepf, Sven J Saupe, Beat H Meier, Roland Riek
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4d95b330bb97425cb7b5d1d55a63b52a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4d95b330bb97425cb7b5d1d55a63b52a
record_format	dspace
spelling	oai:doaj.org-article:4d95b330bb97425cb7b5d1d55a63b52a2021-11-18T05:37:18ZThe mechanism of toxicity in HET-S/HET-s prion incompatibility.1544-91731545-788510.1371/journal.pbio.1001451https://doaj.org/article/4d95b330bb97425cb7b5d1d55a63b52a2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23300377/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885The HET-s protein from the filamentous fungus Podospora anserina is a prion involved in a cell death reaction termed heterokaryon incompatibility. This reaction is observed at the point of contact between two genetically distinct strains when one harbors a HET-s prion (in the form of amyloid aggregates) and the other expresses a soluble HET-S protein (96% identical to HET-s). How the HET-s prion interaction with HET-S brings about cell death remains unknown; however, it was recently shown that this interaction leads to a relocalization of HET-S from the cytoplasm to the cell periphery and that this change is associated with cell death. Here, we present detailed insights into this mechanism in which a non-toxic HET-s prion converts a soluble HET-S protein into an integral membrane protein that destabilizes membranes. We observed liposomal membrane defects of approximately 10 up to 60 nm in size in transmission electron microscopy images of freeze-fractured proteoliposomes that were formed in mixtures of HET-S and HET-s amyloids. In liposome leakage assays, HET-S has an innate ability to associate with and disrupt lipid membranes and that this activity is greatly enhanced when HET-S is exposed to HET-s amyloids. Solid-state nuclear magnetic resonance (NMR) analyses revealed that HET-s induces the prion-forming domain of HET-S to adopt the β-solenoid fold (previously observed in HET-s) and this change disrupts the globular HeLo domain. These data indicate that upon interaction with a HET-s prion, the HET-S HeLo domain partially unfolds, thereby exposing a previously buried ∼34-residue N-terminal transmembrane segment. The liberation of this segment targets HET-S to the membrane where it further oligomerizes, leading to a loss of membrane integrity. HET-S thus appears to display features that are reminiscent of pore-forming toxins.Carolin SeuringJason GreenwaldChristian WasmerRoger WepfSven J SaupeBeat H MeierRoland RiekPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 10, Iss 12, p e1001451 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Carolin Seuring Jason Greenwald Christian Wasmer Roger Wepf Sven J Saupe Beat H Meier Roland Riek The mechanism of toxicity in HET-S/HET-s prion incompatibility.
description	The HET-s protein from the filamentous fungus Podospora anserina is a prion involved in a cell death reaction termed heterokaryon incompatibility. This reaction is observed at the point of contact between two genetically distinct strains when one harbors a HET-s prion (in the form of amyloid aggregates) and the other expresses a soluble HET-S protein (96% identical to HET-s). How the HET-s prion interaction with HET-S brings about cell death remains unknown; however, it was recently shown that this interaction leads to a relocalization of HET-S from the cytoplasm to the cell periphery and that this change is associated with cell death. Here, we present detailed insights into this mechanism in which a non-toxic HET-s prion converts a soluble HET-S protein into an integral membrane protein that destabilizes membranes. We observed liposomal membrane defects of approximately 10 up to 60 nm in size in transmission electron microscopy images of freeze-fractured proteoliposomes that were formed in mixtures of HET-S and HET-s amyloids. In liposome leakage assays, HET-S has an innate ability to associate with and disrupt lipid membranes and that this activity is greatly enhanced when HET-S is exposed to HET-s amyloids. Solid-state nuclear magnetic resonance (NMR) analyses revealed that HET-s induces the prion-forming domain of HET-S to adopt the β-solenoid fold (previously observed in HET-s) and this change disrupts the globular HeLo domain. These data indicate that upon interaction with a HET-s prion, the HET-S HeLo domain partially unfolds, thereby exposing a previously buried ∼34-residue N-terminal transmembrane segment. The liberation of this segment targets HET-S to the membrane where it further oligomerizes, leading to a loss of membrane integrity. HET-S thus appears to display features that are reminiscent of pore-forming toxins.
format	article
author	Carolin Seuring Jason Greenwald Christian Wasmer Roger Wepf Sven J Saupe Beat H Meier Roland Riek
author_facet	Carolin Seuring Jason Greenwald Christian Wasmer Roger Wepf Sven J Saupe Beat H Meier Roland Riek
author_sort	Carolin Seuring
title	The mechanism of toxicity in HET-S/HET-s prion incompatibility.
title_short	The mechanism of toxicity in HET-S/HET-s prion incompatibility.
title_full	The mechanism of toxicity in HET-S/HET-s prion incompatibility.
title_fullStr	The mechanism of toxicity in HET-S/HET-s prion incompatibility.
title_full_unstemmed	The mechanism of toxicity in HET-S/HET-s prion incompatibility.
title_sort	mechanism of toxicity in het-s/het-s prion incompatibility.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/4d95b330bb97425cb7b5d1d55a63b52a
work_keys_str_mv	AT carolinseuring themechanismoftoxicityinhetshetsprionincompatibility AT jasongreenwald themechanismoftoxicityinhetshetsprionincompatibility AT christianwasmer themechanismoftoxicityinhetshetsprionincompatibility AT rogerwepf themechanismoftoxicityinhetshetsprionincompatibility AT svenjsaupe themechanismoftoxicityinhetshetsprionincompatibility AT beathmeier themechanismoftoxicityinhetshetsprionincompatibility AT rolandriek themechanismoftoxicityinhetshetsprionincompatibility AT carolinseuring mechanismoftoxicityinhetshetsprionincompatibility AT jasongreenwald mechanismoftoxicityinhetshetsprionincompatibility AT christianwasmer mechanismoftoxicityinhetshetsprionincompatibility AT rogerwepf mechanismoftoxicityinhetshetsprionincompatibility AT svenjsaupe mechanismoftoxicityinhetshetsprionincompatibility AT beathmeier mechanismoftoxicityinhetshetsprionincompatibility AT rolandriek mechanismoftoxicityinhetshetsprionincompatibility
_version_	1718424846866579456

The mechanism of toxicity in HET-S/HET-s prion incompatibility.

Ejemplares similares