Structural basis for the antifolding activity of a molecular chaperone

Nature. 2016 Sep 8;537(7619):202-206. doi: 10.1038/nature18965. Epub 2016 Aug 8.


Molecular chaperones act on non-native proteins in the cell to prevent their aggregation, premature folding or misfolding. Different chaperones often exert distinct effects, such as acceleration or delay of folding, on client proteins via mechanisms that are poorly understood. Here we report the solution structure of SecB, a chaperone that exhibits strong antifolding activity, in complex with alkaline phosphatase and maltose-binding protein captured in their unfolded states. SecB uses long hydrophobic grooves that run around its disk-like shape to recognize and bind to multiple hydrophobic segments across the length of non-native proteins. The multivalent binding mode results in proteins wrapping around SecB. This unique complex architecture alters the kinetics of protein binding to SecB and confers strong antifolding activity on the chaperone. The data show how the different architectures of chaperones result in distinct binding modes with non-native proteins that ultimately define the activity of the chaperone.

MeSH terms

  • Alkaline Phosphatase / chemistry
  • Alkaline Phosphatase / metabolism
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism*
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / metabolism
  • Hydrophobic and Hydrophilic Interactions
  • Kinetics
  • Maltose-Binding Proteins / chemistry
  • Maltose-Binding Proteins / metabolism
  • Models, Molecular
  • Molecular Chaperones / chemistry*
  • Molecular Chaperones / metabolism*
  • Protein Aggregates*
  • Protein Binding
  • Protein Folding*
  • Protein Unfolding
  • Substrate Specificity


  • Bacterial Proteins
  • Escherichia coli Proteins
  • Maltose-Binding Proteins
  • Molecular Chaperones
  • Protein Aggregates
  • SecB protein, Bacteria
  • Alkaline Phosphatase
  • phoA protein, E coli