Outer membrane targeting of secretin PulD protein relies on disordered domain recognition by a dedicated chaperone

J Biol Chem. 2011 Nov 11;286(45):38833-43. doi: 10.1074/jbc.M111.279851. Epub 2011 Aug 30.


Interaction of bacterial outer membrane secretin PulD with its dedicated lipoprotein chaperone PulS relies on a disorder-to-order transition of the chaperone binding (S) domain near the PulD C terminus. PulS interacts with purified S domain to form a 1:1 complex. Circular dichroism, one-dimensional NMR, and hydrodynamic measurements indicate that the S domain is elongated and intrinsically disordered but gains secondary structure upon binding to PulS. Limited proteolysis and mass spectrometry identified the 28 C-terminal residues of the S domain as a minimal binding site with low nanomolar affinity for PulS in vitro that is sufficient for outer membrane targeting of PulD in vivo. The region upstream of this binding site is not required for targeting or multimerization and does not interact with PulS, but it is required for secretin function in type II secretion. Although other secretin chaperones differ substantially from PulS in sequence and secondary structure, they have all adopted at least superficially similar mechanisms of interaction with their cognate secretins, suggesting that intrinsically disordered regions facilitate rapid interaction between secretins and their chaperones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Outer Membrane Proteins / chemistry*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism
  • Bacterial Secretion Systems / physiology
  • Escherichia coli / chemistry*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Lipoproteins / chemistry
  • Lipoproteins / genetics
  • Lipoproteins / metabolism
  • Molecular Chaperones / chemistry*
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Protein Folding*
  • Protein Structure, Quaternary
  • Protein Structure, Secondary
  • Protein Structure, Tertiary


  • Bacterial Outer Membrane Proteins
  • Bacterial Secretion Systems
  • Escherichia coli Proteins
  • Lipoproteins
  • Molecular Chaperones
  • PulD protein, E coli
  • PulS protein, E coli