TY - JOUR TI - Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast AU - Johnson, Courtney R AU - Steingesser, Marc G AU - Weems, Andrew D AU - Khan, Anum AU - Gladfelter, Amy AU - Bertin, Aurélie AU - McMurray, Michael A A2 - Akhmanova, Anna A2 - Farkasovsky, Marian VL - 9 PY - 2020 DA - 2020/01/28 SP - e54355 C1 - eLife 2020;9:e54355 DO - 10.7554/eLife.54355 UR - https://doi.org/10.7554/eLife.54355 AB - 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. KW - septins KW - oligomerization KW - protein folding KW - guanidine KW - chaperone JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -