Septin Filaments: How to Assemble A Molecular Jigsaw

Speaker: Professor Richard Garratt, São Carlos Institute of Physics (IFSC), University of São Paulo

Host: Roberto Steiner

Abstract: Septins have been considered to be the fourth (and somewhat neglected) filamentous component of the cytoskeleton. They are GTP-binding proteins which play important roles in membrane remodelling events (including cell division) and diffusion barrier formation. 13 human septins form heteropolymeric filaments based on rod-like particles composed of either six or eight monomers. Their spontaneous assembly involves the formation of four or five different interfaces made between homologous molecules - a non-trivial problem in molecular recognition. We have recently shown that a model for the order of the septins along the rod-like particle, which has persisted in the literature for over a decade, is incorrect. This requires rethinking the mechanisms by which filaments self-assemble. We will provide data on how the dynamics at the central interface of the rod likely controls membrane association. We will also describe the discovery of a completely novel coiled coil present in the terminal subunit of the rod (septin 2) and its role in filament assembly and in the formation of higher-order complexes. Off-target cleavage of the coiled-coil domain of septin 2 by Zika virus protease, NS2B-NS3, has been recently shown to be the likely mechanism by which the virus attenuates cell proliferation and ultimately leads to cell death in neural progenitor cells. Septin complexes incorporating a truncated version of septin 2, lacking the coiled coil, fail to polymerize.   

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