Structural and functional model for ionic (K(+)/Na(+)) and pH dependence of GTPase activity and polymerization of FtsZ, the prokaryotic ortholog of tubulin

J Mol Biol. 2009 Jul 3;390(1):17-25. doi: 10.1016/j.jmb.2009.05.018. Epub 2009 May 15.

Abstract

Bacterial cell division occurs through the formation of a protein ring (division ring) at the site of division, with FtsZ being its main component in most bacteria. FtsZ is the prokaryotic ortholog of eukaryotic tubulin; it shares GTPase activity properties and the ability to polymerize in vitro. To study the mechanism of action of FtsZ, we used molecular dynamics simulations of the behavior of the FtsZ dimer in the presence of GTP-Mg(2+) and monovalent cations. The presence of a K(+) ion at the GTP binding site allows the positioning of one water molecule that interacts with catalytic residues Asp235 and Asp238, which are also involved in the coordination sphere of K(+). This arrangement might favor dimer stability and GTP hydrolysis. Contrary to this, Na(+) destabilizes the dimer and does not allow the positioning of the catalytic water molecule. Protonation of the GTP gamma-phosphate, simulating low pH, excludes both monovalent cations and the catalytic water molecule from the GTP binding site and stabilizes the dimer. These molecular dynamics predictions were contrasted experimentally by analyzing the GTPase and polymerization activities of purified Methanococcus jannaschii and Escherichia coli FtsZ proteins in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism*
  • Cytoskeletal Proteins / chemistry*
  • Cytoskeletal Proteins / metabolism*
  • Dimerization
  • Escherichia coli / chemistry*
  • GTP Phosphohydrolases / chemistry*
  • GTP Phosphohydrolases / metabolism*
  • Guanosine Triphosphate / metabolism
  • Methanococcus / chemistry*
  • Models, Molecular
  • Potassium / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Sodium / metabolism*

Substances

  • Bacterial Proteins
  • Cytoskeletal Proteins
  • FtsZ protein, Bacteria
  • Guanosine Triphosphate
  • Sodium
  • GTP Phosphohydrolases
  • Potassium