Single tryptophan mutants of FtsZ: nucleotide binding/exchange and conformational transitions

Biochim Biophys Acta. 2014 Jul;1844(7):1193-200. doi: 10.1016/j.bbapap.2014.03.012. Epub 2014 Apr 2.

Abstract

Cell division protein FtsZ cooperatively self-assembles into straight filaments when bound to GTP. A set of conformational changes that are linked to FtsZ GTPase activity are involved in the transition from straight to curved filaments that eventually disassemble. In this work, we characterized the fluorescence of single Trp mutants as a reporter of the predicted conformational changes between the GDP- and GTP-states of Escherichia coli FtsZ. Steady-state fluorescence characterization showed the Trp senses different environments and displays low solvent accessibility. Time-resolved fluorescence data indicated that the main conformational changes in FtsZ occur at the interaction surface between the N and C domains, but also minor rearrangements were detected in the bulk of the N domain. Surprisingly, despite its location near the bottom protofilament interface at the C domain, the Trp 275 fluorescence lifetime did not report changes between the GDP and GTP states. The equilibrium unfolding of FtsZ features an intermediate that is stabilized by the nucleotide bound in the N-domain as well as by quaternary protein-protein interactions. In this context, we characterized the unfolding of the Trp mutants using time-resolved fluorescence and phasor plot analysis. A novel picture of the structural transition from the native state in the absence of denaturant, to the solvent-exposed unfolded state is presented. Taken together our results show that conformational changes between the GDP and GTP states of FtsZ, such as those observed in FtsZ unfolding, are restricted to the interaction surface between the N and C domains.

Keywords: Conformational change; Equilibrium unfolding; FtsZ; Phasor plot; Time-resolved fluorescence; Tryptophan fluorescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Circular Dichroism
  • Cytoskeletal Proteins / chemistry*
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Guanosine Diphosphate / chemistry
  • Guanosine Diphosphate / metabolism*
  • Guanosine Triphosphate / chemistry
  • Guanosine Triphosphate / metabolism*
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Mutation / genetics*
  • Protein Conformation
  • Protein Folding
  • Spectrometry, Fluorescence
  • Tryptophan / genetics*

Substances

  • Bacterial Proteins
  • Cytoskeletal Proteins
  • FtsZ protein, Bacteria
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • Tryptophan