Inter-domain dynamics in the chaperone SurA and multi-site binding to its outer membrane protein clients

Nat Commun. 2020 May 1;11(1):2155. doi: 10.1038/s41467-020-15702-1.

Abstract

The periplasmic chaperone SurA plays a key role in outer membrane protein (OMP) biogenesis. E. coli SurA comprises a core domain and two peptidylprolyl isomerase domains (P1 and P2), but its mechanisms of client binding and chaperone function have remained unclear. Here, we use chemical cross-linking, hydrogen-deuterium exchange mass spectrometry, single-molecule FRET and molecular dynamics simulations to map the client binding site(s) on SurA and interrogate the role of conformational dynamics in OMP recognition. We demonstrate that SurA samples an array of conformations in solution in which P2 primarily lies closer to the core/P1 domains than suggested in the SurA crystal structure. OMP binding sites are located primarily in the core domain, and OMP binding results in conformational changes between the core/P1 domains. Together, the results suggest that unfolded OMP substrates bind in a cradle formed between the SurA domains, with structural flexibility between domains assisting OMP recognition, binding and release.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism*
  • Binding Sites
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Mass Spectrometry
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Peptidylprolyl Isomerase / genetics
  • Peptidylprolyl Isomerase / metabolism*
  • Protein Binding

Substances

  • Bacterial Outer Membrane Proteins
  • Carrier Proteins
  • Escherichia coli Proteins
  • Molecular Chaperones
  • SurA protein, E coli
  • Peptidylprolyl Isomerase