Fast antibody fragment motion: flexible linkers act as entropic spring

Sci Rep. 2016 Mar 29:6:22148. doi: 10.1038/srep22148.

Abstract

A flexible linker region between three fragments allows antibodies to adjust their binding sites to an antigen or receptor. Using Neutron Spin Echo Spectroscopy we observed fragment motion on a timescale of 7 ns with motional amplitudes of about 1 nm relative to each other. The mechanistic complexity of the linker region can be described by a spring model with Brownian motion of the fragments in a harmonic potential. Displacements, timescale, friction and force constant of the underlying dynamics are accessed. The force constant exhibits a similar strength to an entropic spring, with friction of the fragment matching the unbound state. The observed fast motions are fluctuations in pre-existing equilibrium configurations. The Brownian motion of domains in a harmonic potential is the appropriate model to examine functional hinge motions dependent on the structural topology and highlights the role of internal forces and friction to function.

MeSH terms

  • Algorithms*
  • Binding Sites
  • Entropy
  • Friction
  • Humans
  • Immunoglobulin Fragments / chemistry*
  • Immunoglobulin Fragments / metabolism
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / metabolism
  • Molecular Dynamics Simulation*
  • Motion
  • Neutron Diffraction
  • Protein Binding
  • Protein Domains*
  • Scattering, Small Angle
  • X-Ray Diffraction

Substances

  • Immunoglobulin Fragments
  • Immunoglobulin G