Conformation and dynamics of the periplasmic membrane-protein-chaperone complexes OmpX-Skp and tOmpA-Skp

Nat Struct Mol Biol. 2013 Nov;20(11):1265-72. doi: 10.1038/nsmb.2677. Epub 2013 Sep 29.


The biogenesis of integral outer-membrane proteins (OMPs) in Gram-negative bacteria requires molecular chaperones that prevent the aggregation of OMP polypeptides in the aqueous periplasmic space. How these energy-independent chaperones interact with their substrates is not well understood. We have used high-resolution NMR spectroscopy to examine the conformation and dynamics of the Escherichia coli periplasmic chaperone Skp and two of its complexes with OMPs. The Skp trimer constitutes a flexible architectural scaffold that becomes more rigid upon substrate binding. The OMP substrates populate a dynamic conformational ensemble with structural interconversion rates on the submillisecond timescale. The global lifetime of the chaperone-substrate complex is seven orders of magnitude longer, emerging from the short local lifetimes by avidity. The dynamic state allows for energy-independent substrate release and provides a general paradigm for the conformation of OMP polypeptides bound to energy-independent chaperones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Outer Membrane Proteins / chemistry*
  • Bacterial Outer Membrane Proteins / metabolism*
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism*
  • Escherichia coli / chemistry*
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism*
  • Hydrolases / chemistry*
  • Hydrolases / metabolism*
  • Magnetic Resonance Spectroscopy
  • Models, Biological
  • Models, Molecular
  • Molecular Chaperones / chemistry*
  • Molecular Chaperones / metabolism*
  • Molecular Dynamics Simulation
  • Protein Conformation
  • Time Factors


  • Bacterial Outer Membrane Proteins
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • Molecular Chaperones
  • Skp protein, E coli
  • OmpX protein, E coli
  • OMPA outer membrane proteins
  • Hydrolases