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SEPT9 binds actin through a novel binding motif
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SEPT9 binds actin through a novel binding motif

Rebecca A. Rhodes
Master of Science (M.S.), Drexel University
Aug 2020
DOI:
https://doi.org/10.17918/00000297
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Abstract

Septins Cancer Cytoskeleton
The cytoskeleton is a complex and dynamic structure composed of multiple polymerizing protein networks. Septins are one such network. Since their initial discovery as important proteins needed for cytokinesis in budding yeast, research has implicated septins in a wide variety of mammalian cellular processes. Of these proteins, SEPT9 (SEPT9) is linked to a large number of diverse cancers. The SEPT9 N-terminal domain (NTD) has been found to strongly interact with microtubules and actin. While it is known that the SEPT9 NTD binds actin, SEPT9 does not contain any known actin binding motifs and the nature of this interaction is unknown. Here, we developed a structural mechanism for the understanding the SEPT9 NTD interaction with actin. Using a fluorescence anisotropy-based assay, we identified the extreme N-terminal region of the NTD as responsible for most of SEPT9's actin filament affinity. In addition, we found the NTD was capable of binding actin monomer with similar affinity to actin filament. The discovery of the actin binding region in SEPT9 has implications for how it may interact with other cytoskeletal proteins and may explain how SEPT9 isoform differences impact cancer pathogenesis.

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