Odorant Receptor 7D4 Activation Dynamics.

Published

Journal Article

Deciphering how an odorant activates an odorant receptor (OR) and how changes in specific OR residues affect its responsiveness are central to understanding our sense of smell. A joint approach combining site-directed mutagenesis and functional assays with computational modeling has been used to explore the signaling mechanics of OR7D4. In this OR, a genetic polymorphism affects our perception of androstenone. Molecular simulations totaling 0.12 ms predicted that, similarly to observations for other G-protein-coupled receptors with known experimental structures, an activation pathway connects the ligand and the G-protein binding site. The 3D model activation mechanism correlates with in vitro data and notably predicts that the OR7D4 WM variant is not activated. Upon activation, an OR-specific sequence motif is the convergence point of the mechanism. Our study suggests that robust homology modeling can serve as a powerful tool to capture OR dynamics related to smell perception.

Full Text

Duke Authors

Cited Authors

  • de March, CA; Topin, J; Bruguera, E; Novikov, G; Ikegami, K; Matsunami, H; Golebiowski, J

Published Date

  • April 16, 2018

Published In

Volume / Issue

  • 57 / 17

Start / End Page

  • 4554 - 4558

PubMed ID

  • 29462498

Pubmed Central ID

  • 29462498

Electronic International Standard Serial Number (EISSN)

  • 1521-3773

Digital Object Identifier (DOI)

  • 10.1002/anie.201713065

Language

  • eng

Conference Location

  • Germany