Structure and Biochemical Studies on Sept7

Septins constitute a family of conserved guanine nucleotide binding proteins found in a wide range of organisms from fungi to mammals. Septins were first identified in S. cerevisiae as genes essential for cytokinesis. In higher eukaryotic organisms they have additionally roles in cytoskeletal organization and membrane remodelling. All members of this family share a canonical G-domain with N- and C-terminal extensions. G-domains assemble into hetero-oligomeric non-polarised complexes which in turn polymerize to filaments or rings. There are two different interaction interfaces between the G domains using either the guanine nucleotide binding site (G-interface) or N- and C-terminal extensions (NC-interface).

Septins bind and hydrolyse GTP, but the role of the nucleotide switching for their function is still unknown. To better understand the contribution of the nucleotide state of septins on the structure and dynamics of septin filaments we performed structural and biochemical studies on Sept7, which is a unique septin isoform believed to be responsible for filament formation and breakage. We solved the crystal structure of a Sept7 dimer in the GDP-bound state. The structure and biochemistry of Sept7 provide new insights into the dynamic of G-Interface and show the clear differences in the properties of Sept7 compared to the members of Group 2 as well as the members of Group 6.