Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast
- University of Colorado Anschutz Medical Campus, United States
- University of North Carolina at Chapel Hill, United States
- Institut Curie, France
Abstract
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.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Michael A McMurray
Funding
National Institute of General Medical Sciences (R00GM086603)
- Michael A McMurray
National Institute of General Medical Sciences (R01GM124024)
- Michael A McMurray
Alzheimer's Association (NIRGD-12-241119)
- Michael A McMurray
Rare Genomics Institute (BeHEARD Initiative)
- Michael A McMurray
Agence Nationale de la Recherche (ANR-10-INSB-04)
- Aurélie Bertin
Agence Nationale de la Recherche (ANR-10-LBX-0038)
- Aurélie Bertin
National Science Foundation (MCB-1615138)
- Anum Khan
- Amy Galdfelter
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Johnson et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast
eLife 9:e54355.
https://doi.org/10.7554/eLife.54355
