Deciphering the odorant binding protein - olfactory receptor interactions

Year: 2015

DOI: 10.1093/chemse/bju073

Olfactory receptors (OR) belong to the family of GPCR and
participate to the recognition of odorants. Prior to the activation
of the OR, odorants are disolved in the olfactory mucus
by odorant binding proteins (OBP). Belonging to the family
of lipocalins, they are small carrier proteins and are considered
as non-specific binders. OBP would contribute to the olfaction
process by carrying hydrophobic odorant molecules to the
OR. Due to the transmembrane nature of these receptors, it
remains a hard task to obtain their crystal structure. Molecular
modeling methods are perfectly suited to provide relevant
three-dimensional models of unknown structures to further
gain insights on the structural features of protein-protein complexes.
Molecular models of hOR2T4 and rORI7 have been
built using both ab initio homology modeling approaches.
To understand how OBPs release odorants and participate to
the modulation of OR activation, state of the art protein-protein
docking [4] have been performed to predict OR-OBP complexes
structure (Figure 1). We propose models of interactions
showing how rOBP3 is connected to the extracellular loop 2
of hORI7. To decipher the underlying molecular mechanism,
molecular dynamics simulations have been carried out to estimate
the octanal-rOBP3 free energy of binding. The formation
of the OBP-OR complex destabilizes the odorant-OBP interactions
prior to the release of the odorant.