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- W2969463356 abstract "ABSTRACT Septin proteins co-assemble into hetero-oligomers that polymerize into cytoskeletal filaments with a variety of cellular functions. In Saccharomyces cerevisiae , where septins were first discovered, five subunits comprise two species of septin hetero-octamers, Cdc11/Shs1–Cdc12–Cdc3–Cdc10– Cdc10–Cdc3–Cdc12–Cdc11/Shs1. Septins evolved from ancestral GTPases. We previously found evidence that slow GTPase activity by Cdc12 directs the choice of incorporation of Cdc11 vs Shs1 into septin complexes. It was unclear why many septins, including Cdc3, lack GTPase activity. We serendipitously discovered that the small molecule guanidine hydrochloride (GdnHCl) 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 ion (Gdm) occupies the site of a “missing” Arg sidechain that is present in other fungal species in which (i) the Cdc3 subunit is an active GTPase and (ii) Cdc10-less hexamers co-exist with octamers in wild-type cells. These findings support a model in which Gdm reactivates a latent septin assembly pathway that was suppressed during fungal evolution in order to restrict assembly to hetero-octamers. Given that septin hexamers made natively in human cells also exclude Cdc10-like central subunits via homodimerization of an active GTPase, our results provide new mechanistic details that likely apply to septin assembly throughout phylogeny." @default.
- W2969463356 created "2019-08-29" @default.
- W2969463356 creator A5013371396 @default.
- W2969463356 creator A5014458109 @default.
- W2969463356 creator A5059374123 @default.
- W2969463356 creator A5060163973 @default.
- W2969463356 creator A5069819026 @default.
- W2969463356 creator A5078040703 @default.
- W2969463356 creator A5082887631 @default.
- W2969463356 date "2019-08-24" @default.
- W2969463356 modified "2023-10-01" @default.
- W2969463356 title "Guanidine hydrochloride reactivates an ancient septin hetero-oligomer assembly pathway in budding yeast" @default.
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