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The ganglioside GM1 interacts with the serotonin 1A receptor via the sphingolipid binding domain.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2016 Nov; Vol. 1858 (11), pp. 2818-2826. Date of Electronic Publication: 2016 Aug 20. - Publication Year :
- 2016
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Abstract
- Glycosphingolipids are minor yet essential components of eukaryotic cell membranes and are involved in a variety of cellular processes. Although glycosphingolipids such as GM1 have been previously reported to influence the function of G protein-coupled receptors (GPCRs), the molecular mechanism remains elusive. In this paper, we have explored the interaction of GM1 with the serotonin <subscript>1A</subscript> receptor, an important neurotransmitter receptor that belongs to the GPCR family. To examine the molecular basis of the interaction of GM1 with the serotonin <subscript>1A</subscript> receptor, we performed a series of coarse-grain molecular dynamics simulations of the receptor embedded in membrane bilayers containing GM1. Our results show that GM1 interacts with the serotonin <subscript>1A</subscript> receptor predominantly at the extracellular loop 1 and specifically at the sphingolipid binding domain (SBD). The SBD motif consists of a characteristic combination of aromatic, basic and turn-inducing residues, and is evolutionarily conserved in case of the serotonin <subscript>1A</subscript> receptor. The interaction of the SBD site with GM1 appears to stabilize a 'flip-out' conformation in which W102 of the extracellular loop 1 flips out from the central lumen of the receptor toward the membrane. The population of the 'flip-out' conformation is increased in the presence of cholesterol. Our data strongly suggest that a direct interaction between GM1 and the SBD site of the serotonin <subscript>1A</subscript> receptor may occur in vivo. In view of the reported role of GM1 and the serotonin <subscript>1A</subscript> receptor in neurodegenerative diseases, GM1-receptor interaction assumes significance in the context of malfunctioning of neuronal GPCRs under such conditions.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1858
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 27552916
- Full Text :
- https://doi.org/10.1016/j.bbamem.2016.08.009