Presentation Details
| Stable by design: what ligand binding reveals about the function of odorant-binding proteins in mammals? Jérémie Topin1, Maxence Lalis1, Christine Belloir2, Loïc Briand2, Cornelia Meinert1. 1Institut de Chimie de Nice, UMR CNRS 7272, Université Côte d'Azur, Nice, France.2Centre des Sciences du Goût et de l’Alimentation, CNRS, INRAE, Institut Agro, Université de Bourgogne, Dijon, France |
Abstract
Mammalian odorant-binding proteins (OBPs) belong to the lipocalin family and are widely expressed in the olfactory epithelium, where they are commonly associated with olfaction. However, despite the availability of high-resolution structures, their precise physiological role in olfaction remains poorly defined, and it is still unclear whether OBPs are directly involved in odour recognition or rather play an ancillary role in odour processing. To investigate the molecular basis of ligand interaction with OBPs and its functional implications, we adopted an integrative approach combining molecular modelling, network analysis, site-directed mutagenesis, isothermal titration calorimetry (ITC), and synchrotron circular dichroism (CD) spectroscopy. We show that ligand entry occurs without inducing major conformational changes or destabilization of the protein, in both wild-type and mutant OBPs. Allosteric pathways modulate ligand access and affinity, yet the overall protein fold remains preserved throughout the binding process. This high stability argues against a direct role of OBPs in odor recognition, which typically relies on dynamic structural rearrangements. Instead, our results support a role for OBPs as robust scavenger or buffering proteins that capture, retain, and regulate the availability of odorant molecules[1]. Importantly, this intrinsic stability, combined with conserved ligand-entry mechanisms across the lipocalin family, makes OBPs particularly attractive as biological sensing elements for bio-nose applications, where durability, reproducibility, and sustained ligand binding are essential. [1]M. Lalis, et al. How Allosteric Mutations Control Ligand Binding in Lipocalin Protein: Odorant Binding Protein as a Test Case, Cellular and Molecular Life Science, 2025.
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