Nature Research, Nature Structural and Molecular Biology, 11(20), p. 1265-1272, 2013
DOI: 10.1038/nsmb.2677
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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.