Proceedings of the 47th Annual Meeting of the Brazilian Biophysical Society

Septins are cytoskeletal proteins that serve as important scaffold components within cells. In humans, there are 13 different septins, some of which possess a C-terminal domain (CTD) containing coiled-coil (CC) repeats. Filament formation involves the end-to-end association of heterooctamers and/or heterohexamers, such as SEPT2-6-7-(9-9)-7-6-2. Notably, it is postulated that closely related septins can substitute for one another in the same relative position within filaments; for instance, SEPT8/10/11/14 might replace SEPT6. Despite considerable advancements in understanding septin structure [1], certain aspects remain uncharacterized. Specifically, the structural properties of their heterodimeric coiled coil, along with its long known interaction with the BORG's BD3 (BORG homology domain) motif [2], have yet to be fully elucidated. In this study, we present the X-ray structure of the SEPT14-SEPT7 heterodimeric CC. Additionally, we investigate the interaction between the SEPT6-SEPT7 CC and a BD3 peptide of BORG3. Remarkably, the structure of the SEPT14-SEPT7 CC exhibits a distinctive parallel arrangement, featuring two distinct CC periodicities: heptads and hendecads. The N-terminal portion of the hendecad region proves crucial for heterodimerization, suggesting a potential role in septin molecular recognition. Furthermore, supported by AlphaFold modeling predictions, we establish that this region within the heterodimeric CC serves as the binding site for BD3. These versatile CTDs facilitate the formation of both parallel-heterodimer and antiparallel-homodimer CC arrangements and represent a hotspot for interaction with partners.