Identification of Sphingolipid-binding Motif in G Protein-coupled Receptors
Sphingolipids correspond to a major class of lipids which serve as indispensable structural components of membranes and play an important role in various cellular functions. They constitute ~10–20% of total membrane lipids and are known to form segregated domains in biological membranes. Sphingolipids have been shown to play a vital role in the function of various G protein-coupled receptors (GPCRs). We report here the presence of sphingolipid-binding motif (SBM) in representative GPCRs such as cholecystokinin, oxytocin and secretin receptors, and subtypes of human serotonin receptors. We previously reported the importance of sphingolipids in the function of the serotonin1A receptor, a representative member of the GPCR superfamily, involved in behavioral, cognitive, and developmental functions. In this work, we show that the serotonin1A receptor contains a putative SBM, corresponding to amino acids 205 to 213. In addition, our analysis shows that SBM is an intrinsic characteristic feature of the serotonin1A receptor and is conserved throughout the course of natural evolution. Our results represent the first report on the presence of SBM in serotonin1A receptors and provide novel insight on the molecular mechanism of GPCR-sphingolipid interaction.
KeywordsSBM Sphingolipids GPCR Serotonin1A receptor CRAC
Cholesterol recognition/interaction amino acid consensus
G protein-coupled receptor
This work was supported by the Science and Engineering Research Board (Govt. of India) project (EMR/2016/002294). A.C. gratefully acknowledges J.C. Bose Fellowship from the Department of Science and Technology, Govt. of India. A.C. is an Adjunct Professor of Tata Institute of Fundamental Research (Mumbai), RMIT University (Melbourne, Australia), Indian Institute of Technology (Kanpur), and Indian Institute of Science Education and Research (Mohali). We thank members of the Chattopadhyay laboratory for critically reading the manuscript.