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 that FtsA-FtsZ co-localization at the septum of dividing bacteria is essential for successful cell division in E. coli. We have validated and characterized 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 interaction of S. aureus FtsZ. These observations are consistent with the conserved role of FtsA and FtsZ in bacterial cell division. Using deletion mutagenesis, we have shown that a highly conserved motif as small as 10 residues in the extreme C-terminus of S. aureus FtsZ is critical for the interaction with FtsA. Further dissection of this motif by alanine scanning mutagenesis showed that Phe376 likely plays a major role in the FtsA-FtsZ interaction. This work has important implications for the design of antagonists and agonists of the FtsA-FtsZ interaction as such agents could provide a novel approach for tackling multi-resistant Gram positive pathogens.
Yan
K
K
SmithKline Beecham Pharmaceuticals, Anti-infectives Research Department, UP1345, 1250 S. Collegeville Road, Collegeville, Pennsylvania 19426, USA. Kang_Yan-1@sbphrd.com
Pearce
K H
KH
Payne
D J
DJ
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D003001:Cloning, Molecular; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins; D016297:Mutagenesis, Site-Directed; D017386:Sequence Homology, Amino Acid; D013211:Staphylococcus aureus / Q000378:metabolism*
D001426:Bacterial Proteins; D003598:Cytoskeletal Proteins; D029968:Escherichia coli Proteins; C065103:FtsA protein, Bacteria; C489310:FtsA protein, E coli; C071525:FtsZ protein, Bacteria