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FtsA is a bacterial protein that is related to actin by overall structural similarity and in its ATP binding pocket. It is involved in bacterial cell division, where it serves to tether the cytokinetic ring formed by FtsZ to the cytoplasmic membrane prior to division.
Along with other bacterial actin homologs such as MreB, ParM, and MamK, these proteins suggest that eukaryotic actin has a common ancestry. Like the other bacterial actins, FtsA binds ATP and can form actin-like filaments. The FtsA-FtsA interface has been defined by structural as well as genetic analysis. Although present in many diverse Gram-positive and Gram-negative species, FtsA is absent in Actinomycetota and cyanobacteria. FtsA also is structurally similar to PilM, a type IV pilus ATPase.
Although FtsA is essential for viability in E. coli, it can be deleted in B. subtilis. B. subtilis cells lacking FtsA divide poorly but still survive. Another FtsZ-interacting protein, SepF (originally named YlmF; ), is able to replace FtsA in B. subtilis, suggesting that SepF and FtsA have overlapping functions.
An allele of FtsA called FtsA* (R286W) is able to bypass the normal requirement for the ZipA in E. coli cytokinesis. FtsA* also causes cells to divide at a shorter cell length than normal, suggesting that FtsA may normally receive signals from the septum synthesis machinery to regulate when cytokinesis can proceed. Other FtsA*-like alleles have been found, and they mostly decrease FtsA-FtsA interactions. Oligomeric state of FtsA is likely important for regulating its activity, its ability to recruit the later cell division proteins and its ability to bind ATP. Other cell division proteins of E. coli, including FtsN and the ABC transporter homologs FtsEX, seem to regulate septum constriction by signaling through FtsA, and the FtsQLB subcomplex is also involved in promoting FtsN-mediated septal constriction. FtsA binds directly to the conserved C-terminal domain of FtsZ. This FtsA-FtsZ interaction is likely involved in regulating FtsZ polymer dynamics. In vitro, E. coli FtsA disassembles FtsZ polymers in the presence of ATP, both in solution, as FtsA* and on supported lipid bilayers. E. coli FtsA itself does not assemble into detectable structures except when on membranes, where it forms dodecameric minirings that often pack in clusters and bind to single FtsZ protofilaments. In contrast, FtsA* forms arcs on lipid membranes but rarely closed minirings, supporting genetic evidence that this mutant has a weaker FtsA-FtsA interface. When bound to the membrane, FtsA*-like mutants, which also can form double-stranded filaments, enhance close lateral interactions between FtsZ protofilaments, in contrast to FtsA, which keeps FtsZ protofilaments apart. As FtsZ protofilament bundling may be important for promoting septum formation, a switch from an FtsA-like to an FtsA*-like conformation during cell cycle progression may serve to turn on septum synthesis enzymes (FtsWI) as well as condense FtsZ polymers, setting up a positive feedback loop. In support of this model, the cytoplasmic domain of FtsN, which activates FtsWI in E. coli and interacts directly with the 1C subdomain of FtsA, switches FtsA from the miniring form to the double stranded filament form on lipid surfaces in vitro. These double filaments of E. coli FtsA are antiparallel, indicating that they themselves do not treadmill like FtsZ filaments.
Although E. coli FtsA has been the most extensively studied, more is becoming understood about FtsA proteins from other species. FtsA from Streptococcus pneumoniae forms helical filaments in the presence of ATP, but no interactions with FtsZ in vitro have been reported yet. FtsA colocalizes with FtsZ in S. pneumoniae, but also is required for FtsZ ring localization, in contrast to E. coli where FtsZ rings remain localized upon inactivation of FtsA. FtsA from Staphylococcus aureus forms actin-like filaments similar to those of FtsA from Thermotoga maritima. In addition, S. aureus FtsA enhances the GTPase activity of FtsZ. In a liposome system, FtsA* stimulates FtsZ to form rings that can divide liposomes, mimicking cytokinesis in vitro.
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