title: A gain-of-function mutation in ftsA bypasses the requirement for the essential cell division gene zipA in Escherichia coli.
abstract: ZipA and FtsA are recruited independently to the FtsZ cytokinetic ring (Z ring) and are essential for cell division of Escherichia coli. The molecular role of FtsA in cell division is unknown; however, ZipA is thought to stabilize the Z ring, anchor it to the membrane, and recruit downstream cell division proteins. Here we demonstrate that the requirement for ZipA can be bypassed completely by a single alteration in a conserved residue of FtsA (FtsA*). Cells with ftsA* in single copy in place of WT ftsA or with ftsA* alone on a multicopy plasmid divide mostly normally, whether they are zipA+ or zipA-. Experiments with ftsQAZ and ftsQA*Z on multicopy plasmids indicate that ftsQAZzipA+ and ftsQA*ZzipA- cells divide fairly normally, whereas ftsQAZzipA- cells divide poorly and ftsQA*ZzipA+ cells display a phenotype that suggests their septa are unusually stable. In support of the idea that ftsA* stabilizes Z rings, single-copy ftsA* confers resistance to excess MinC, which destabilizes Z rings. The inhibitory effect of excess ZipA on division is also suppressed by ftsA*. These results suggest that the molecular mechanism of the FtsA* bypass is to stabilize FtsZ assembly via a parallel pathway and that FtsA* can replace the multiple functions of ZipA. This is an example of a complete functional replacement of an essential prokaryotic cell division protein by another and may explain why most bacteria can divide without an obvious ZipA homolog.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Texas Medical School, 6431 Fannin Street, Houston, TX 77030, USA.
authors.forename: Brett
authors.initials: B
authors.lastname: Geissler
authors.forename: Dany
authors.initials: D
authors.lastname: Elraheb
authors.forename: William
authors.initials: W
authors.lastname: Margolin
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics*; D002455:Cell Division / Q000235:genetics*; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000166:cytology / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics; D020043:Genes, Essential; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010957:Plasmids; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D029968:Escherichia coli Proteins; D011994:Recombinant Proteins; C103795:ZipA protein, E coli