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Identification of Sphingolipid-binding Motif in G Protein-coupled Receptors

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Biochemical and Biophysical Roles of Cell Surface Molecules

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1112))

Abstract

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.

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Abbreviations

CRAC:

Cholesterol recognition/interaction amino acid consensus

GPCR:

G protein-coupled receptor

SBM:

Sphingolipid-binding motif

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Acknowledgments

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.

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Authors and Affiliations

  1. CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India

    Sandeep Shrivastava, Md. Jafurulla, Shrish Tiwari & Amitabha Chattopadhyay

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  1. Sandeep Shrivastava
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  2. Md. Jafurulla
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  3. Shrish Tiwari
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  4. Amitabha Chattopadhyay
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Correspondence to Amitabha Chattopadhyay .

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Editors and Affiliations

  1. Centre for Protein Science, Design and Engineering, Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Mohali, Punjab, India

    Kausik Chattopadhyay

  2. Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, USA

    Subhash C. Basu

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Shrivastava, S., Jafurulla, M., Tiwari, S., Chattopadhyay, A. (2018). Identification of Sphingolipid-binding Motif in G Protein-coupled Receptors. In: Chattopadhyay, K., Basu, S. (eds) Biochemical and Biophysical Roles of Cell Surface Molecules. Advances in Experimental Medicine and Biology, vol 1112. Springer, Singapore. https://doi.org/10.1007/978-981-13-3065-0_10

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