Cargando…
Theme and variations: evolutionary diversification of the HET-s functional amyloid motif
In mammals and fungi, Nod-like receptors (NLR) activate downstream cell death execution proteins by a prion-like mechanism. In Podospora anserina, the NWD2 NLR activates the HET-S Helo-domain pore-forming protein by converting its prion-forming domain into a characteristic β-solenoid amyloid fold. T...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518210/ https://www.ncbi.nlm.nih.gov/pubmed/26219477 http://dx.doi.org/10.1038/srep12494 |
_version_ | 1782383304470691840 |
---|---|
author | Daskalov, Asen Dyrka, Witold Saupe, Sven J. |
author_facet | Daskalov, Asen Dyrka, Witold Saupe, Sven J. |
author_sort | Daskalov, Asen |
collection | PubMed |
description | In mammals and fungi, Nod-like receptors (NLR) activate downstream cell death execution proteins by a prion-like mechanism. In Podospora anserina, the NWD2 NLR activates the HET-S Helo-domain pore-forming protein by converting its prion-forming domain into a characteristic β-solenoid amyloid fold. The amyloid forming region of HET-S/s comprises two repetitions of a 21 amino acid motif. Herein, we systematically analyze the sequences of C-terminal regions of fungal HeLo and HeLo-like domain proteins to identify HET-s-related amyloid motifs (HRAM). We now identify four novel HRAM subfamilies in addition to the canonical HET-S/s subfamily. These novel motifs share the pseudo-repeat structure of HET-S/s and a specific pattern of distribution of hydrophobic and polar residues. Sequence co-variance analyses predict parallel in-register β-stacking of the two repeats and residue-residue interactions compatible with the β-solenoid fold. As described for HET-S, most genes encoding the HeLo proteins are adjacent to genes encoding NLRs also displaying HRAMs. The motifs of the NLRs are similar to those of their cognate HeLo-domain protein, indicating concerted evolution between repeats. This study shows that HET-s-related amyloid motifs are more common than anticipated and that they have diversified into discrete subfamilies that apparently share a common overall fold. |
format | Online Article Text |
id | pubmed-4518210 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-45182102015-08-06 Theme and variations: evolutionary diversification of the HET-s functional amyloid motif Daskalov, Asen Dyrka, Witold Saupe, Sven J. Sci Rep Article In mammals and fungi, Nod-like receptors (NLR) activate downstream cell death execution proteins by a prion-like mechanism. In Podospora anserina, the NWD2 NLR activates the HET-S Helo-domain pore-forming protein by converting its prion-forming domain into a characteristic β-solenoid amyloid fold. The amyloid forming region of HET-S/s comprises two repetitions of a 21 amino acid motif. Herein, we systematically analyze the sequences of C-terminal regions of fungal HeLo and HeLo-like domain proteins to identify HET-s-related amyloid motifs (HRAM). We now identify four novel HRAM subfamilies in addition to the canonical HET-S/s subfamily. These novel motifs share the pseudo-repeat structure of HET-S/s and a specific pattern of distribution of hydrophobic and polar residues. Sequence co-variance analyses predict parallel in-register β-stacking of the two repeats and residue-residue interactions compatible with the β-solenoid fold. As described for HET-S, most genes encoding the HeLo proteins are adjacent to genes encoding NLRs also displaying HRAMs. The motifs of the NLRs are similar to those of their cognate HeLo-domain protein, indicating concerted evolution between repeats. This study shows that HET-s-related amyloid motifs are more common than anticipated and that they have diversified into discrete subfamilies that apparently share a common overall fold. Nature Publishing Group 2015-07-29 /pmc/articles/PMC4518210/ /pubmed/26219477 http://dx.doi.org/10.1038/srep12494 Text en Copyright © 2015, Macmillan Publishers Limited 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 Daskalov, Asen Dyrka, Witold Saupe, Sven J. Theme and variations: evolutionary diversification of the HET-s functional amyloid motif |
title | Theme and variations: evolutionary diversification of the HET-s functional amyloid motif |
title_full | Theme and variations: evolutionary diversification of the HET-s functional amyloid motif |
title_fullStr | Theme and variations: evolutionary diversification of the HET-s functional amyloid motif |
title_full_unstemmed | Theme and variations: evolutionary diversification of the HET-s functional amyloid motif |
title_short | Theme and variations: evolutionary diversification of the HET-s functional amyloid motif |
title_sort | theme and variations: evolutionary diversification of the het-s functional amyloid motif |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518210/ https://www.ncbi.nlm.nih.gov/pubmed/26219477 http://dx.doi.org/10.1038/srep12494 |
work_keys_str_mv | AT daskalovasen themeandvariationsevolutionarydiversificationofthehetsfunctionalamyloidmotif AT dyrkawitold themeandvariationsevolutionarydiversificationofthehetsfunctionalamyloidmotif AT saupesvenj themeandvariationsevolutionarydiversificationofthehetsfunctionalamyloidmotif |