ZipA Uses a Two-Pronged FtsZ-Binding Mechanism Necessary for Cell Division.

In most bacteria, cell division is centrally organized by the FtsZ protein, which assembles into dynamic filaments at the division site along the cell membrane that interact with other key cell division proteins. In gammaproteobacteria such as Escherichia coli, FtsZ filaments are anchored to the cell membrane by two essential proteins, FtsA and ZipA. Canonically, this interaction was believed to be mediated solely by the FtsZ C-terminal peptide (CTP) domain that interacts with these and several other regulatory proteins.

Overproduction of a Dominant Mutant of the Conserved Era GTPase Inhibits Cell Division in Escherichia coli.

Cell growth and division are coordinated, ensuring homeostasis under any given growth condition, with division occurring as cell mass doubles. The signals and controlling circuit(s) between growth and division are not well understood; however, it is known in that the essential GTPase Era, which is growth rate regulated, coordinates the two functions and may be a checkpoint regulator of both. We have isolated a mutant of Era that separates its effect on growth and division.

Peptide Linkers within the Essential FtsZ Membrane Tethers ZipA and FtsA Are Nonessential for Cell Division.

Bacteria such as divide by organizing filaments of FtsZ, a tubulin homolog that assembles into dynamic treadmilling membrane-associated protein filaments at the cell midpoint. FtsA and ZipA proteins are required to tether these filaments to the inner face of the cytoplasmic membrane, and loss of either tether is lethal. ZipA from and other closely related species harbors a long linker region that connects the essential N-terminal transmembrane domain to the C-terminal globular FtsZ-binding domain, and part of this linker includes a P/Q-rich peptide that is predicted to be intrinsically disordered.

Direct Interaction between the Two Z Ring Membrane Anchors FtsA and ZipA.

The initiation of cell division requires three proteins, FtsZ, FtsA, and ZipA, which assemble in a dynamic ring-like structure at midcell. Along with the transmembrane protein ZipA, the actin-like FtsA helps to tether treadmilling polymers of tubulin-like FtsZ to the membrane. In addition to forming homo-oligomers, FtsA and ZipA interact directly with the C-terminal conserved domain of FtsZ.

Suppression of a Thermosensitive Cell Division Mutant by Altering Amino Acid Metabolism.

ZipA is essential for cell division in , acting early in the process to anchor polymers of FtsZ to the cytoplasmic membrane. Along with FtsA, FtsZ and ZipA form a proto-ring at midcell that recruits additional proteins to eventually build the division septum. Cells carrying the thermosensitive allele divide fairly normally at 30°C in rich medium but cease dividing at temperatures above 34°C, forming long filaments.

Accumulation of periplasmic enterobactin impairs the growth and morphology of Escherichia coli tolC mutants.

TolC is the outer membrane component of tripartite efflux pumps, which expel proteins, toxins and antimicrobial agents from Gram-negative bacteria. Escherichia coli tolC mutants grow well and are slightly elongated in rich media but grow less well than wild-type cells in minimal media. These phenotypes have no physiological explanation as yet.