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. Gain-of-function mutants of FtsA are deficient in forming oligomers and can bypass the need for ZipA, suggesting that ZipA may normally function to disrupt FtsA oligomers, although no direct interaction between FtsA and ZipA has been reported. Here, we use cross-linking to show that FtsA and ZipA indeed interact directly. We identify the exposed surface of FtsA helix 7, which also participates in binding to ATP through its internal surface, as a key interface needed for the interaction with ZipA. This interaction suggests that FtsZ's membrane tethers may regulate each other's activities. To divide, most bacteria first construct a protein machine at the plane of division and then recruit the machinery that will synthesize the division septum. In , this first stage involves the assembly of FtsZ polymers at midcell, which directly bind to membrane-associated proteins FtsA and ZipA to form a discontinuous ring structure. Although FtsZ directly binds both FtsA and ZipA, it is unclear why FtsZ requires two separate membrane tethers. Here, we uncover a new direct interaction between the tethers, which involves a helix within FtsA that is adjacent to its ATP binding pocket. Our findings imply that in addition to their known roles as FtsZ membrane anchors, FtsA and ZipA may regulate each other's structure and function.