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Odorant Receptor 7D4 Activation Dynamics.

Publication ,  Journal Article
de March, CA; Topin, J; Bruguera, E; Novikov, G; Ikegami, K; Matsunami, H; Golebiowski, J
Published in: Angew Chem Int Ed Engl
April 16, 2018

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.

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Published In

Angew Chem Int Ed Engl

DOI

EISSN

1521-3773

Publication Date

April 16, 2018

Volume

57

Issue

17

Start / End Page

4554 / 4558

Location

Germany

Related Subject Headings

  • Receptors, Odorant
  • Organic Chemistry
  • Molecular Dynamics Simulation
  • Molecular Conformation
  • Humans
  • Crystallography, X-Ray
  • 34 Chemical sciences
  • 03 Chemical Sciences
 

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de March, C. A., Topin, J., Bruguera, E., Novikov, G., Ikegami, K., Matsunami, H., & Golebiowski, J. (2018). Odorant Receptor 7D4 Activation Dynamics. Angew Chem Int Ed Engl, 57(17), 4554–4558. https://doi.org/10.1002/anie.201713065
March, Claire A. de, Jérémie Topin, Elise Bruguera, Gleb Novikov, Kentaro Ikegami, Hiroaki Matsunami, and Jérôme Golebiowski. “Odorant Receptor 7D4 Activation Dynamics.Angew Chem Int Ed Engl 57, no. 17 (April 16, 2018): 4554–58. https://doi.org/10.1002/anie.201713065.
de March CA, Topin J, Bruguera E, Novikov G, Ikegami K, Matsunami H, et al. Odorant Receptor 7D4 Activation Dynamics. Angew Chem Int Ed Engl. 2018 Apr 16;57(17):4554–8.
de March, Claire A., et al. “Odorant Receptor 7D4 Activation Dynamics.Angew Chem Int Ed Engl, vol. 57, no. 17, Apr. 2018, pp. 4554–58. Pubmed, doi:10.1002/anie.201713065.
de March CA, Topin J, Bruguera E, Novikov G, Ikegami K, Matsunami H, Golebiowski J. Odorant Receptor 7D4 Activation Dynamics. Angew Chem Int Ed Engl. 2018 Apr 16;57(17):4554–4558.
Journal cover image

Published In

Angew Chem Int Ed Engl

DOI

EISSN

1521-3773

Publication Date

April 16, 2018

Volume

57

Issue

17

Start / End Page

4554 / 4558

Location

Germany

Related Subject Headings

  • Receptors, Odorant
  • Organic Chemistry
  • Molecular Dynamics Simulation
  • Molecular Conformation
  • Humans
  • Crystallography, X-Ray
  • 34 Chemical sciences
  • 03 Chemical Sciences