Interplay of septin amphipathic helices in sensing membrane-curvature and filament bundling

Woods, Benjamin; Cannon, Kevin S.; Gladfelter, Amy S.

doi:10.1101/2020.05.12.090787

Cited by 2 publications

(2 citation statements)

References 47 publications

(68 reference statements)

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“…To ask if AHs are found outside of opisthokonts and therefore can be an ancestral feature of septins, we developed a high-throughput pipeline to identify AH domains in a large number of polypeptide sequences by predicting alpha helices and then calculating their amphipathicity (see Materials & Methods), and applied it to the NTE and C-terminal extension (CTE) of our eukaryotic septin collection. This pipeline precisely identified previously reported AH domains in fungal and animal septins (Cannon et al, 2019;Lobato-Márquez et al, 2021;Woods et al, 2021), such as Cdc12 and Shs1 in S. cerevisiae and Ashbya gossyppii, human SEPT6, Caenorhabditis elegans UNC-61, and Drosophila melanogaster Sep1 (Fig. S5).…”

Section: Amphipathic Helices Are An Ancestral Feature Of Septinssupporting

confidence: 79%

The Evolutionary Origins and Ancestral Features of Septins

Delic,

Shuman,

Lee

et al. 2024

Preprint

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Septins are a family of membrane-associated cytoskeletal GTPases that play crucial roles in various cellular processes, such as cell division, phagocytosis, and organelle fission. Despite their importance, the evolutionary origins and ancestral function of septins remain unclear. In opisthokonts, septins form five distinct groups of orthologs, with subunits from multiple groups assembling into heteropolymers, thus supporting their diverse molecular functions. Recent studies have revealed that septins are also conserved in algae and protists, indicating an ancient origin from the last eukaryotic common ancestor. However, the phylogenetic relationships among septins across eukaryotes remained unclear. Here, we expanded the list of non-opisthokont septins, including previously unrecognized septins from rhodophyte red algae and glaucophyte algae. Constructing a rooted phylogenetic tree of 254 total septins, we observed a bifurcation between the major non-opisthokont and opisthokont septin clades. Within the non-opisthokont septins, we identified three major subclades: Group 6 representing chlorophyte green algae (6A mostly for species with single septins, 6B for species with multiple septins), Group 7 representing algae in chlorophytes, heterokonts, haptophytes, chrysophytes, and rhodophytes, and Group 8 representing ciliates. Glaucophyte and some ciliate septins formed orphan lineages in-between all other septins and the outgroup. Combining ancestral-sequence reconstruction and AlphaFold predictions, we tracked the structural evolution of septins across eukaryotes. In the GTPase domain, we identified a conserved GAP-like arginine finger within the G-interface of at least one septin in most algal and ciliate species. This residue is required for homodimerization of the singleChlamydomonasseptin, and its loss coincided with septin duplication events in various lineages. The loss of the arginine finger is often accompanied by the emergence of the α0 helix, a known NC-interface interaction motif, potentially signifying the diversification of septin-septin interaction mechanisms from homo-dimerization to hetero-oligomerization. Lastly, we found amphipathic helices in all septin groups, suggesting that curvature-sensing is an ancestral trait of septin proteins. Coiled-coil domains were also broadly distributed, while transmembrane domains were found in some septins in Group 6A and 7. In summary, this study advances our understanding of septin distribution and phylogenetic groupings, shedding light on their ancestral features, potential function, and early evolution.

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Section: Amphipathic Helices Are An Ancestral Feature Of Septinssupporting

confidence: 79%

The Evolutionary Origins and Ancestral Features of Septins

Delic,

Shuman,

Lee

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Previous studies found that under certain conditions, recombinant septin filaments can be paired, possibly through coiled-coil interactions between the C-termini of Cdc3 and Cdc12 (Bertin et al, 2008). However, truncating the coiled-coil of Cdc3 or Cdc12 is lethal, precluding our ability to test this hypothesis in extracts (Finnigan et al, 2015; Woods et al, 2020). Alternatively, filament pairing could be mediated through septin regulators.…”

Section: Resultsmentioning

confidence: 99%

Biophysical properties governing septin assembly

Woods

Seim

Liu

et al. 2021

Preprint

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Septin filaments build structures such as rings, lattices and gauzes that serve as platforms for localizing signaling and organizing cell membranes. How cells control the geometry of septin assemblies in poorly understood. We show here that septins are isodesmic polymers, in contrast to cooperative polymerization exhibited by F-actin and microtubules. We constructed a physical model to analyze and interpret how septin assemblies change in the presence of regulators in yeast extracts. Notably filaments differ in length and curvature in yeast extract compared to pure protein indicating cellular regulators modulate intrinsic biophysical features. Combining analysis of extracts from regulatory mutants with simulations, we found increased filament flexibility and reduced filament fragmentation promote assembly of septin rings, whereas reduced flexibility in crowded environments promotes local filament alignment. This work demonstrates how tuning of intrinsic features of septin filament assembly by regulatory proteins yields a diverse array of structures observed in cells.

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Interplay of septin amphipathic helices in sensing membrane-curvature and filament bundling

Cited by 2 publications

References 47 publications

The Evolutionary Origins and Ancestral Features of Septins

The Evolutionary Origins and Ancestral Features of Septins

Biophysical properties governing septin assembly

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