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How broadly tuned olfactory receptors equally recognize their agonists. Human OR1G1 as a test case

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Abstract

The molecular features that dominate the binding mode of agonists by a broadly tuned olfactory receptor are analyzed through a joint approach combining cell biology, calcium imaging, and molecular modeling. The odorant/receptor affinities, estimated through statistics accrued during molecular dynamics simulations, are in accordance with the experimental ranking. Although in many systems receptors recognize their target through a network of oriented interactions, such as H-bonding, the binding by broadly tuned olfactory receptors is dominated by non-polar terms. We show how such a feature allows chemicals belonging to different chemical families to similarly activate the receptors through compensations of interactions within the binding site.

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Note added in proof

A recent article reports a model of hOR1G1 [37]. Their model and our both put forward equivalent residues for the binding cavity. For example, their bound structure of 1-nonanol corresponds to one of our initial structures.

Acknowledgments

The CINES provided computer time. JG acknowledges the University of Nice Sophia Antipolis for funding the project Olfactome. Dr. Steffen Wolf and Pr. Klaus Gerwert are acknowledged for sending the structure of hOR2AG1. Dr. Ravinder Abrol helped in GPCR ab initio modeling.

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Author notes

  1. Landry Charlier

    Present address: Institut des Biomolécules Max Mousseron, CNRS-UMR 5247, Faculté de Pharmacie, Université Montpellier 1, Université Montpellier 2, 15 Avenue Charles Flahault, BP 14491, 34093, Montpellier Cedex 5, France

Authors and Affiliations

  1. Institut de Chimie de Nice, UMR CNRS, Université de Nice Sophia Antipolis 7272, 06108, Nice Cedex 2, France

    Landry Charlier, Jérémie Topin & Jérôme Golebiowski

  2. Laboratoire de Neuroglycobiologie, GLM, CNRS, 31 Ch. J. Aiguier, 13402, Marseille, France

    Catherine Ronin

  3. Materials and Process Simulation Center (MC139-74), California Institute of Technology, 1200 E. California Blvd., Pasadena, CA, 91125, USA

    Soo-Kyung Kim & William A. Goddard III

  4. Laboratory of Biomolecular Modeling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya, 16/10, 117997, Moscow, Russia

    Roman Efremov

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  1. Landry Charlier
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Correspondence to Jérôme Golebiowski.

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Charlier, L., Topin, J., Ronin, C. et al. How broadly tuned olfactory receptors equally recognize their agonists. Human OR1G1 as a test case. Cell. Mol. Life Sci. 69, 4205–4213 (2012). https://doi.org/10.1007/s00018-012-1116-0

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  • DOI: https://doi.org/10.1007/s00018-012-1116-0

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