Visualizing chaperone-assisted protein folding

Nat Struct Mol Biol. 2016 Jul;23(7):691-7. doi: 10.1038/nsmb.3237. Epub 2016 May 30.

Abstract

Challenges in determining the structures of heterogeneous and dynamic protein complexes have greatly hampered past efforts to obtain a mechanistic understanding of many important biological processes. One such process is chaperone-assisted protein folding. Obtaining structural ensembles of chaperone-substrate complexes would ultimately reveal how chaperones help proteins fold into their native state. To address this problem, we devised a new structural biology approach based on X-ray crystallography, termed residual electron and anomalous density (READ). READ enabled us to visualize even sparsely populated conformations of the substrate protein immunity protein 7 (Im7) in complex with the Escherichia coli chaperone Spy, and to capture a series of snapshots depicting the various folding states of Im7 bound to Spy. The ensemble shows that Spy-associated Im7 samples conformations ranging from unfolded to partially folded to native-like states and reveals how a substrate can explore its folding landscape while being bound to a chaperone.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Crystallography, X-Ray / methods
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Gene Expression
  • Kinetics
  • Molecular Dynamics Simulation
  • Periplasmic Proteins / chemistry*
  • Periplasmic Proteins / genetics
  • Periplasmic Proteins / metabolism
  • Protein Binding
  • Protein Folding*
  • Protein Interaction Domains and Motifs
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Thermodynamics

Substances

  • Carrier Proteins
  • E colicin-binding immunity protein Im7, E coli
  • Escherichia coli Proteins
  • Periplasmic Proteins
  • Recombinant Proteins
  • Spy protein, E coli