The NMR structure of FliK, the trigger for the switch of substrate specificity in the flagellar type III secretion apparatus

J Mol Biol. 2011 Jun 17;409(4):558-73. doi: 10.1016/j.jmb.2011.04.008. Epub 2011 Apr 12.

Abstract

The flagellar cytoplasmic protein FliK controls hook elongation by two successive events: by determining hook length and by stopping the supply of hook protein. These two distinct roles are assigned to different parts of FliK: the N-terminal half (FliK(N)) determines length and the C-terminal half (FliK(C)) switches secretion from the hook protein to the filament protein. The interaction of FliK(C) with FlhB, the switchable secretion gate, triggers the switch. By NMR spectroscopy, we demonstrated that FliK is largely unstructured and determined the structure of a compact domain in FliK(C). The compact domain, denoted the FliK(C) core domain, consists of two α-helices, a β-sheet with two parallel and two antiparallel strands, and several exposed loops. Based on the functional data obtained by a series of deletion mutants of the FliK(C) core domain, we constructed a model of the complex between the FliK(C) core domain and FlhB(C). The model suggested that one of the FliK(C) loops has a high probability of interacting with the C-terminal domain of FlhB (FlhB(C)) as the FliK molecule enters the secretion gate. We suggest that the autocleaved NPTH sequence in FlhB contacts loop 2 of FliK(C) to trigger the switching event. This contact is sterically prevented when NPTH is not cleaved. Thus, the structure of FliK provides insight into the mechanism by which this bifunctional protein triggers a switch in the export of substrates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Flagella / metabolism
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Structure, Secondary
  • Protein Structure, Tertiary*
  • Sequence Alignment
  • Substrate Specificity*

Substances

  • Bacterial Proteins
  • FlhB protein, Bacteria
  • FliK protein, Bacteria
  • Membrane Proteins
  • Protein Isoforms

Associated data

  • PDB/2RRL