A conserved residue at the extreme C-terminus of FtsZ is critical for the FtsA-FtsZ interaction in Staphylococcus aureus

FtsZ, a tubulin-like protein with GTPase activity, and FtsA, an actin-like protein with ATPase activity, are two proteins known to play critical roles in the later stages of the bacterial cell cycle. It is well documented tha t FtsA-FtsZ co-localization at the septum of dividing bacteria is essential for successful cell division in E. coli, We have validated and characteriz ed this interaction by co-expressing FtsA and FtsZ, from both E. coli and S . aureus, in the yeast two-hybrid system. We demonstrate for the first time a specific association between S. aureus FtsA and FtsZ proteins and self i nteraction of S, aureus FtsZ. These observations are consistent with the co nserved role of FtsA and FtsZ in bacterial cell division. Using deletion mu tagenesis, we have shown that a highly conserved motif as small as 10 resid ues in the extreme C-terminus of S. aureus FtsZ is critical for the interac tion with FtsA. Further dissection of this motif by alanine scanning mutage nesis showed that Phe376 likely plays a major role in the FtsA-FtsZ interac tion. This work has important implications for the design of antagonists an d agonists of the FtsA-FtsZ interaction as such agents could provide a nove l approach for tackling multiresistant Gram positive pathogens. (C) 2000 Ac ademic Press.