• Citer

How lipids influence the activity of β2-adrenergic receptor

par Dawaliby, Rosie ;Manglik, Aashish;Grimard, Vinciane ;Trubbia, Cataldo ;Van Antwerpen, Pierre ;Sunahara, Roger;Kobilka, Brian K.
Référence GPCR Workshop 2013(Decembre 1-5 2013: Maui, Hawaï), How lipids influence the activity of β2-adrenergic receptor
Publication Publié, 2013-12

Abstract de conférence

• Détails
• Contenu

Résumé :

The lipidic composition of the membrane bilayer has been proven to be a critical player in the modulation of many membrane protein structure and function. Several studies have proposed a functional role for lipids, especially cholesterol, on the biological behavior of GPCRs. Our studies will focus on the human b2-adrenergic receptor (b2AR), which is involved mostly in the modulation of the sympathetic nervous system. Since b2AR is widely expressed in the organism, the question of the receptor regulation in different tissues arises. It has been suggested that a tissue-specific regulation of b2AR is possible in relation to its environment. The effect of cholesterol on b2AR stability and function has been clearly shown in some publications. However, very few studies tackle the role of other membrane lipids on GPCRs activity. Thus our work was aimed to understand the effect of lipids on b2AR function. We have developed a method to examine the interaction between lipids in biological membranes and the receptor using mass spectrometry. We were thus able to identify the lipid species bound to the purified receptor. We have also tested the effect of lipid environment on the functionality of the receptor. Using different lipid species individually, we have reconstituted b2AR in HDL particles of phosphatidylcholine (PC), phosphatydilethanolamine (PE), phosphatidylglycerol (PG), phosphatydylserine (PS), PC/Cholesteryl hemisuccinate (PC/CHS) and PC/sphingomyelin (PC/SM). We show the choice of lipids strongly modulate the affinity of the receptor towards its ligands as well as liguand-induced conformational changes. Some lipid species, like PE favor an inactive state of the receptor, whereas others like PG promote the activation of the protein. Cholesterol analogue CHS enhances the affinity of b2AR towards its ligands (agonist and antagonist). We have also monitored the effect of fatty acid chain length on the receptor activity.The results presented here constitute a significant step towards understanding the relationship between b2AR and the lipids in biological membrane.