Description

FtsZ is the organizer for cell division in most bacteria, where it forms the Z-ring that recruits the other divisomal proteins. FtsZ monomers assemble into protofilaments that can associate laterally in different fashions. How FtsZ filaments organize in the dynamic division ring is still a challenging problem. Rather than forming a well-defined structure, such as band or tubule, FtsZ filaments laterally associate among them in a relatively disordered fashion, and bind partner and regulatory proteins, including those tethering them to the inner face of the plasma membrane. FtsZ filaments made of FtsZ monomers laterally associate in solution through the disordered C-terminal tails, forming loose bundles; we think that these self-organizing properties of FtsZ underlie the assembly of the bacterial division ring (Huecas 2017).

Several GTP analogues selectively inhibit FtsZ polymerization but support tubulin assembly, revealing exploitable differences between the GTP binding sites of both proteins (Marcelo 2013). We have replaced GTP by synthetic molecules that modulate FtsZ assembly, inhibiting the correct Z-ring formation, bacterial cell division and the growth of several antibiotic-resistant pathogens (Ruiz-Avila 2013). 

Cooperative assembly of single-stranded FtsZ filaments involves self-switching of FtsZ monomers from the closed interdomain cleft conformation into an open-cleft conformation with enhanced association interface between monomer, as shown by crystal structures of each conformation (Wagstaff, 2017). The effective antibacterial compound PC190723 binds into the interdomain cleft, allosterically stabilizing FtsZ filaments. We have developed fluorescent probes that bind into the open cleft (Artola et al., 2017) and can be employed to find allosteric inhibitors of FtsZ.  Synthetic developmental regulator MciZ targets FtsZ and inhibits bacterial division (Araujo-Bazán 2019)

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