Role of protein dynamics in transmembrane receptor signalling

Curr Opin Struct Biol. 2018 Feb:48:74-82. doi: 10.1016/j.sbi.2017.10.017. Epub 2017 Nov 11.

Abstract

Cells are dependent on transmembrane receptors to communicate and transform chemical and physical signals into intracellular responses. Because receptors transport 'information', conformational changes and protein dynamics play a key mechanistic role. We here review examples where experiment and computation have been used to study receptor dynamics. Recent studies on three distinct classes of receptors (G-protein coupled receptors, ligand-gated ion-channels and single-pass receptors) are highlighted to show that conformational changes across a range of time-scales and length-scales are central to function. Because the receptors function in a heterogeneous environment and need to be able to switch between distinct functional states, they may be particularly sensitive to small perturbations that complicate studies linking dynamics to function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Eukaryotic Cells / metabolism
  • Eukaryotic Cells / ultrastructure
  • Humans
  • Ligand-Gated Ion Channels / chemistry*
  • Ligand-Gated Ion Channels / physiology
  • Ligands
  • Molecular Dynamics Simulation
  • Protein Conformation
  • Receptor Protein-Tyrosine Kinases / chemistry*
  • Receptor Protein-Tyrosine Kinases / physiology
  • Receptors, Cytokine / chemistry*
  • Receptors, Cytokine / physiology
  • Receptors, G-Protein-Coupled / chemistry*
  • Receptors, G-Protein-Coupled / physiology
  • Signal Transduction / physiology*
  • Structure-Activity Relationship

Substances

  • Ligand-Gated Ion Channels
  • Ligands
  • Receptors, Cytokine
  • Receptors, G-Protein-Coupled
  • Receptor Protein-Tyrosine Kinases