Dissecting the Binding Interface of the Septin Polymerization Enhancer Borg BD3.

Area of Science:

• Cell Biology
• Molecular Biology
• Protein Interactions

Background:

• Septin filaments are essential for various cellular functions, often requiring interaction with membranes or cytoskeleton.
• The precise mechanisms by which septins interact with their binding partners remain largely unknown.

Purpose of the Study:

• To elucidate the role of C-terminal domains in septin polymerization.
• To characterize the molecular interaction between septins and the BD3 motif of Borg proteins.
• To understand how binding partners influence septin filament assembly.

Main Methods:

• Detailed molecular-level description of the BD3-septin interaction.
• Analysis of ternary complex formation involving SEPT6, SEPT7, and BD3.
• Experimental validation of structural models.

Main Results:

• The C-terminal domains of septins are essential for polymerization and Borg BD3 motif association.
• Ternary complex formation stabilizes the septin heterodimeric coiled coil.
• Borg proteins promote septin filament assembly under non-permissive ionic conditions, favoring hexamers.
• Structural models reveal antiparallel positioning of BD3 to the coiled coil, stabilized by polar and apolar contacts.
• A conserved LGPS motif in Borg proteins interacts with charged residues in SEPT6 and SEPT7, indicating a universal binding mechanism.

Conclusions:

• Septin C-terminal domains are key regulators of both polymerization and binding to Borg proteins.
• Borg proteins can modulate septin filament assembly and disassembly in vivo.
• A conserved molecular mechanism governs Borg-septin interactions, involving specific charge and hydrophobic contacts.