Abstract

G Protein-Coupled receptors represent the main communicating pathway for signals from the outside to the inside of most of eukaryotic cells. They define the largest family of integral membrane receptors at the surface of the cells and constitute the main target of the current drugs on the market. The low affinity leukotriene receptor BLT2 is a receptor involved in pro- and anti-inflammatory pathways and can be activated by various unsaturated fatty acid compounds. We present here the NMR structure of the agonist 12–HHT in its BLT2-bound state and a model of interaction of the ligand with the receptor based on a conformational homology modeling associated with docking simulations. Put into perspective with the data obtained with leukotriene B4, our results illuminate the ligand selectivity of BLT2 and may help define new molecules to modulate the activity of this receptor.

Details

Title
Structure of the agonist 12–HHT in its BLT2 receptor-bound state
Author
Giusti Fabrice 1   VIAFID ORCID Logo  ; Casiraghi, Marina 2 ; Point Elodie 3 ; Damian, Marjorie 4 ; Rieger Jutta 5 ; Bon, Christel Le 3 ; Pozza Alexandre 3 ; Moncoq Karine 3 ; Jean-Louis, Banères 4 ; Catoire, Laurent J 3 

1  Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS/Université de Paris, Institut de Biologie Physico–Chimique (FRC 550), Paris, France (GRID:grid.450875.b) (ISNI:0000 0004 0643 538X); Institut de Chimie Séparative de Marcoule, ICSM UMR 5257, Site de Marcoule, Bâtiment 426, BP 17171, Bagnols sur Cèze Cedex, France (GRID:grid.462049.d) (ISNI:0000 0004 0384 1091) 
2  Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS/Université de Paris, Institut de Biologie Physico–Chimique (FRC 550), Paris, France (GRID:grid.450875.b) (ISNI:0000 0004 0643 538X); Stanford University School of Medicine, Department of Molecular and Cellular Physiology, Stanford California, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
3  Laboratoire de Biologie Physico-Chimique des Protéines Membranaires, UMR 7099, CNRS/Université de Paris, Institut de Biologie Physico–Chimique (FRC 550), Paris, France (GRID:grid.450875.b) (ISNI:0000 0004 0643 538X) 
4  Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS, Université Montpellier, ENSCM, Montpellier, France (GRID:grid.462008.8) 
5  Institut Parisien de Chimie Moléculaire, Sorbonne Université, CNRS, UMR 8232, Equipe Chimie des Polymères, Paris Cedex, France (GRID:grid.4444.0) (ISNI:0000 0001 2112 9282) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-020-59571-6
ProQuest document ID
2355273654
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.