GTPase activity of mycobacterial FtsZ is impaired due to its transphosphorylation by the eukaryotic-type Ser/Thr kinase, PknA

J Biol Chem. 2006 Dec 29;281(52):40107-13. doi: 10.1074/jbc.M607216200. Epub 2006 Oct 26.

Abstract

FtsZ, a homolog of eukaryotic tubulin, is involved in the process of cell division, particularly in septum formation in bacteria. The primary amino acid sequences of this protein are fairly conserved in prokaryotes. We observed that a eukaryotic-type Ser/Thr protein kinase, PknA from Mycobacterium tuberculosis, when expressed in Escherichia coli exhibited cell elongation due to a defect in septum formation. We found that FtsZ either from Escherichia coli (eFtsZ) or from M. tuberculosis (mFtsZ) was phosphorylated on co-expression with PknA. Consistent with these observations, solid phase binding and in vitro kinase assays revealed the ability of PknA to interact with mFtsZ protein and also to phosphorylate it. We, therefore, ascertained mFtsZ as a substrate of PknA. Furthermore, the phosphorylated mFtsZ exhibited impairment in its GTP hydrolysis and polymerization abilities. Thus, our results highlighted the ability of PknA to phosphorylate as well as to regulate the functionality of FtsZ, the protein central to cell division throughout the bacterial lineage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / biosynthesis
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Bacterial Proteins / physiology*
  • Cytokinesis / genetics
  • Cytokinesis / physiology
  • Cytoskeletal Proteins / antagonists & inhibitors*
  • Cytoskeletal Proteins / metabolism*
  • Cytoskeletal Proteins / physiology
  • Escherichia coli / cytology
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • GTP Phosphohydrolases / antagonists & inhibitors
  • GTP Phosphohydrolases / metabolism*
  • GTP Phosphohydrolases / physiology
  • Genetic Vectors
  • Growth Inhibitors / biosynthesis
  • Growth Inhibitors / genetics
  • Growth Inhibitors / physiology
  • Mycobacterium tuberculosis / cytology
  • Mycobacterium tuberculosis / enzymology*
  • Mycobacterium tuberculosis / genetics
  • Phosphorylation
  • Protein Interaction Mapping
  • Protein-Serine-Threonine Kinases / biosynthesis
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / metabolism

Substances

  • Bacterial Proteins
  • Cytoskeletal Proteins
  • FtsZ protein, Bacteria
  • Growth Inhibitors
  • Recombinant Proteins
  • PknA protein, Mycobacterium tuberculosis
  • Protein-Serine-Threonine Kinases
  • GTP Phosphohydrolases