A Spring-Loaded Mechanism Governs the Clamp-like Dynamics of the Skp Chaperone

Structure. 2017 Jul 5;25(7):1079-1088.e3. doi: 10.1016/j.str.2017.05.018. Epub 2017 Jun 22.

Abstract

The trimeric periplasmic holdase chaperone Skp binds and stabilizes unfolded outer membrane proteins (OMPs) as part of bacterial OMP biogenesis. Skp binds client proteins in its central cavity, thereby reducing its backbone dynamics, but the molecular mechanisms that govern Skp dynamics and adaptation to differently sized clients remains unknown. Here, we employ a combination of microsecond timescale molecular dynamics simulation, small-angle X-ray scattering, and nuclear magnetic resonance spectroscopy to reveal that Skp is remarkably flexible, and features a molecular spring-loaded mechanism in its "tentacle" arms that enables switching between two distinct conformations on sub-millisecond timescales. The conformational switch is executed around a conserved pivot element within the coiled-coil structures of the tentacles, allowing expansion of the cavity and thus accommodation of differently sized clients. The spring-loaded mechanism shows how a chaperone can efficiently modulate its structure and function in an ATP-independent manner.

Keywords: NMR spectroscopy; OMPs; SAXS; Skp chaperone; molecular dynamics (MD) simulations; outer membrane proteins; small-angle X-ray scattering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism
  • Magnetic Resonance Spectroscopy
  • Molecular Chaperones / chemistry*
  • Molecular Chaperones / metabolism
  • Molecular Dynamics Simulation*
  • Scattering, Small Angle
  • X-Rays

Substances

  • Bacterial Outer Membrane Proteins
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • Molecular Chaperones
  • Skp protein, E coli
  • Adenosine Triphosphate