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Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast
Septin proteins evolved from ancestral GTPases and co-assemble into hetero-oligomers and cytoskeletal filaments. In Saccharomyces cerevisiae, five septins comprise two species of hetero-octamers, Cdc11/Shs1–Cdc12–Cdc3–Cdc10–Cdc10–Cdc3–Cdc12–Cdc11/Shs1. Slow GTPase activity by Cdc12 directs the choic...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056273/ https://www.ncbi.nlm.nih.gov/pubmed/31990274 http://dx.doi.org/10.7554/eLife.54355 |
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author | Johnson, Courtney R Steingesser, Marc G Weems, Andrew D Khan, Anum Gladfelter, Amy Bertin, Aurélie McMurray, Michael A |
author_facet | Johnson, Courtney R Steingesser, Marc G Weems, Andrew D Khan, Anum Gladfelter, Amy Bertin, Aurélie McMurray, Michael A |
author_sort | Johnson, Courtney R |
collection | PubMed |
description | Septin proteins evolved from ancestral GTPases and co-assemble into hetero-oligomers and cytoskeletal filaments. In Saccharomyces cerevisiae, five septins comprise two species of hetero-octamers, Cdc11/Shs1–Cdc12–Cdc3–Cdc10–Cdc10–Cdc3–Cdc12–Cdc11/Shs1. Slow GTPase activity by Cdc12 directs the choice of incorporation of Cdc11 vs Shs1, but many septins, including Cdc3, lack GTPase activity. We serendipitously discovered that guanidine hydrochloride rescues septin function in cdc10 mutants by promoting assembly of non-native Cdc11/Shs1–Cdc12–Cdc3–Cdc3–Cdc12–Cdc11/Shs1 hexamers. We provide evidence that in S. cerevisiae Cdc3 guanidinium occupies the site of a ‘missing’ Arg side chain found in other fungal species where (i) the Cdc3 subunit is an active GTPase and (ii) Cdc10-less hexamers natively co-exist with octamers. We propose that guanidinium reactivates a latent septin assembly pathway that was suppressed during fungal evolution in order to restrict assembly to octamers. Since homodimerization by a GTPase-active human septin also creates hexamers that exclude Cdc10-like central subunits, our new mechanistic insights likely apply throughout phylogeny. |
format | Online Article Text |
id | pubmed-7056273 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-70562732020-03-05 Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast Johnson, Courtney R Steingesser, Marc G Weems, Andrew D Khan, Anum Gladfelter, Amy Bertin, Aurélie McMurray, Michael A eLife Biochemistry and Chemical Biology Septin proteins evolved from ancestral GTPases and co-assemble into hetero-oligomers and cytoskeletal filaments. In Saccharomyces cerevisiae, five septins comprise two species of hetero-octamers, Cdc11/Shs1–Cdc12–Cdc3–Cdc10–Cdc10–Cdc3–Cdc12–Cdc11/Shs1. Slow GTPase activity by Cdc12 directs the choice of incorporation of Cdc11 vs Shs1, but many septins, including Cdc3, lack GTPase activity. We serendipitously discovered that guanidine hydrochloride rescues septin function in cdc10 mutants by promoting assembly of non-native Cdc11/Shs1–Cdc12–Cdc3–Cdc3–Cdc12–Cdc11/Shs1 hexamers. We provide evidence that in S. cerevisiae Cdc3 guanidinium occupies the site of a ‘missing’ Arg side chain found in other fungal species where (i) the Cdc3 subunit is an active GTPase and (ii) Cdc10-less hexamers natively co-exist with octamers. We propose that guanidinium reactivates a latent septin assembly pathway that was suppressed during fungal evolution in order to restrict assembly to octamers. Since homodimerization by a GTPase-active human septin also creates hexamers that exclude Cdc10-like central subunits, our new mechanistic insights likely apply throughout phylogeny. eLife Sciences Publications, Ltd 2020-01-28 /pmc/articles/PMC7056273/ /pubmed/31990274 http://dx.doi.org/10.7554/eLife.54355 Text en © 2020, Johnson et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry and Chemical Biology Johnson, Courtney R Steingesser, Marc G Weems, Andrew D Khan, Anum Gladfelter, Amy Bertin, Aurélie McMurray, Michael A Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast |
title | Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast |
title_full | Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast |
title_fullStr | Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast |
title_full_unstemmed | Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast |
title_short | Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast |
title_sort | guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast |
topic | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056273/ https://www.ncbi.nlm.nih.gov/pubmed/31990274 http://dx.doi.org/10.7554/eLife.54355 |
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