Odorant binding and conformational dynamics in the odorant-binding protein

J Biol Chem. 2006 Oct 6;281(40):29929-37. doi: 10.1074/jbc.M604869200. Epub 2006 Jul 18.

Abstract

In mammals, the olfactory epithelium secretes odorant-binding proteins (OBPs), which are lipocalins found freely dissolved in the mucus layer protecting the olfactory neurons. OBPs may act as passive transporters of predominantly hydrophobic odorant molecules across the aqueous mucus layer, or they may play a more active role in which the olfactory neuronal receptor recognizes the OBP-ligand complex. To better understand the molecular events accompanying the initial steps in the olfaction process, we have performed molecular dynamics studies of rat and pig OBPs with the odorant molecule thymol. These calculations provide an atomic level description of conformational changes and pathway intermediates that remain difficult to study directly. A series of eight independent molecular dynamics trajectories of rat OBP permitted the observation of a consensus pathway for ligand unbinding and the calculation of the potential of mean force (PMF) along this path. Titration microcalorimetry confirmed the specific binding of thymol to this protein with a strong hydrophobic component. In both rat and pig OBPs we observed lipocalin strand pair opening in the presence of ligand, consistent with potential roles of these proteins in olfactive receptor recognition.

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Ligands
  • Lipocalin 1
  • Protein Binding / physiology
  • Protein Conformation
  • Rats
  • Receptors, Odorant / chemistry*
  • Receptors, Odorant / metabolism*
  • Swine
  • Thermodynamics*
  • Thymol / metabolism*

Substances

  • Carrier Proteins
  • Lcn1 protein, rat
  • Ligands
  • Lipocalin 1
  • Receptors, Odorant
  • odorant-binding protein
  • Thymol