Cargando…
Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a polymerization template for downstream ASC
AIM2 recognizes foreign dsDNA and assembles into the inflammasome, a filamentous supramolecular signalling platform required to launch innate immune responses. We show here that the pyrin domain of AIM2 (AIM2(PYD)) drives both filament formation and dsDNA binding. In addition, the dsDNA-binding doma...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4525163/ https://www.ncbi.nlm.nih.gov/pubmed/26197926 http://dx.doi.org/10.1038/ncomms8827 |
_version_ | 1782384282776371200 |
---|---|
author | Morrone, Seamus R. Matyszewski, Mariusz Yu, Xiong Delannoy, Michael Egelman, Edward H. Sohn, Jungsan |
author_facet | Morrone, Seamus R. Matyszewski, Mariusz Yu, Xiong Delannoy, Michael Egelman, Edward H. Sohn, Jungsan |
author_sort | Morrone, Seamus R. |
collection | PubMed |
description | AIM2 recognizes foreign dsDNA and assembles into the inflammasome, a filamentous supramolecular signalling platform required to launch innate immune responses. We show here that the pyrin domain of AIM2 (AIM2(PYD)) drives both filament formation and dsDNA binding. In addition, the dsDNA-binding domain of AIM2 also oligomerizes and assists in filament formation. The ability to oligomerize is critical for binding dsDNA, and in turn permits the size of dsDNA to regulate the assembly of the AIM2 polymers. The AIM2(PYD) oligomers define the filamentous structure, and the helical symmetry of the AIM2(PYD) filament is consistent with the filament assembled by the PYD of the downstream adaptor ASC. Our results suggest that the role of AIM2(PYD) is not autoinhibitory, but generating a structural template by coupling ligand binding and oligomerization is a key signal transduction mechanism in the AIM2 inflammasome. |
format | Online Article Text |
id | pubmed-4525163 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45251632015-09-04 Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a polymerization template for downstream ASC Morrone, Seamus R. Matyszewski, Mariusz Yu, Xiong Delannoy, Michael Egelman, Edward H. Sohn, Jungsan Nat Commun Article AIM2 recognizes foreign dsDNA and assembles into the inflammasome, a filamentous supramolecular signalling platform required to launch innate immune responses. We show here that the pyrin domain of AIM2 (AIM2(PYD)) drives both filament formation and dsDNA binding. In addition, the dsDNA-binding domain of AIM2 also oligomerizes and assists in filament formation. The ability to oligomerize is critical for binding dsDNA, and in turn permits the size of dsDNA to regulate the assembly of the AIM2 polymers. The AIM2(PYD) oligomers define the filamentous structure, and the helical symmetry of the AIM2(PYD) filament is consistent with the filament assembled by the PYD of the downstream adaptor ASC. Our results suggest that the role of AIM2(PYD) is not autoinhibitory, but generating a structural template by coupling ligand binding and oligomerization is a key signal transduction mechanism in the AIM2 inflammasome. Nature Pub. Group 2015-07-22 /pmc/articles/PMC4525163/ /pubmed/26197926 http://dx.doi.org/10.1038/ncomms8827 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Morrone, Seamus R. Matyszewski, Mariusz Yu, Xiong Delannoy, Michael Egelman, Edward H. Sohn, Jungsan Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a polymerization template for downstream ASC |
title | Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a polymerization template for downstream ASC |
title_full | Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a polymerization template for downstream ASC |
title_fullStr | Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a polymerization template for downstream ASC |
title_full_unstemmed | Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a polymerization template for downstream ASC |
title_short | Assembly-driven activation of the AIM2 foreign-dsDNA sensor provides a polymerization template for downstream ASC |
title_sort | assembly-driven activation of the aim2 foreign-dsdna sensor provides a polymerization template for downstream asc |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4525163/ https://www.ncbi.nlm.nih.gov/pubmed/26197926 http://dx.doi.org/10.1038/ncomms8827 |
work_keys_str_mv | AT morroneseamusr assemblydrivenactivationoftheaim2foreigndsdnasensorprovidesapolymerizationtemplatefordownstreamasc AT matyszewskimariusz assemblydrivenactivationoftheaim2foreigndsdnasensorprovidesapolymerizationtemplatefordownstreamasc AT yuxiong assemblydrivenactivationoftheaim2foreigndsdnasensorprovidesapolymerizationtemplatefordownstreamasc AT delannoymichael assemblydrivenactivationoftheaim2foreigndsdnasensorprovidesapolymerizationtemplatefordownstreamasc AT egelmanedwardh assemblydrivenactivationoftheaim2foreigndsdnasensorprovidesapolymerizationtemplatefordownstreamasc AT sohnjungsan assemblydrivenactivationoftheaim2foreigndsdnasensorprovidesapolymerizationtemplatefordownstreamasc |