How membrane lipids control the 3D structure and function of receptors

Jacques Fantini; Francisco J. Barrantes; Jacques Fantini; Francisco J. Barrantes

doi:10.3934/biophy.2018.1.22

AIMS Biophysics

2018, Volume 5, Issue 1: 22-35. doi: 10.3934/biophy.2018.1.22

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How membrane lipids control the 3D structure and function of receptors

Jacques Fantini ^{1
,
,},
Francisco J. Barrantes ²

1.
Aix-Marseille University, INSERM UMR 1072, Boulevard Pierre Dramard, 13015 Marseille, France
2.
Laboratory of Molecular Neurobiology, Institute of Biomedical Research (BIOMED) UCA-CONICET, 1107 Buenos Aires, Argentina

Received: 27 October 2017 Accepted: 31 January 2018 Published: 07 February 2018

The cohabitation of lipids and proteins in the plasma membrane of mammalian cells is controlled by specific biochemical and biophysical rules. Lipids may be either constitutively tightly bound to cell-surface receptors (non-annular lipids) or less tightly attached to the external surface of the protein (annular lipids). The latter are exchangeable with surrounding bulk membrane lipids on a faster time scale than that of non-annular lipids. Not only do non-annular lipids bind to membrane proteins through stereoselective mechanisms, they can also help membrane receptors acquire (or maintain) a functional 3D structure. Cholesterol is the prototype of membrane lipids that finely controls the 3D structure and function of receptors. However, several other lipids such as sphingolipids may also modulate the function of membrane proteins though conformational adjustments. All these concepts are discussed in this review in the light of representative examples taken from the literature.
- cholesterol,
- sphingolipids,
- hopanoids,
- lipid rafts,
- ion channels,
- GPCR
Citation: Jacques Fantini, Francisco J. Barrantes. How membrane lipids control the 3D structure and function of receptors[J]. AIMS Biophysics, 2018, 5(1): 22-35. doi: 10.3934/biophy.2018.1.22

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Abstract

The cohabitation of lipids and proteins in the plasma membrane of mammalian cells is controlled by specific biochemical and biophysical rules. Lipids may be either constitutively tightly bound to cell-surface receptors (non-annular lipids) or less tightly attached to the external surface of the protein (annular lipids). The latter are exchangeable with surrounding bulk membrane lipids on a faster time scale than that of non-annular lipids. Not only do non-annular lipids bind to membrane proteins through stereoselective mechanisms, they can also help membrane receptors acquire (or maintain) a functional 3D structure. Cholesterol is the prototype of membrane lipids that finely controls the 3D structure and function of receptors. However, several other lipids such as sphingolipids may also modulate the function of membrane proteins though conformational adjustments. All these concepts are discussed in this review in the light of representative examples taken from the literature.

References

[1]	Singer SJ, Nicolson GL (1972) The fluid mosaic model of the structure of cell membranes. Science 175: 720–731. doi: 10.1126/science.175.4023.720
[2]	Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387: 569–572. doi: 10.1038/42408
[3]	Sonnino S, Prinetti A (2013) Membrane domains and the "lipid raft" concept. Curr Med Chem 20: 4–21.
[4]	Fantini J (2003) How sphingolipids bind and shape proteins: Molecular basis of lipid-protein interactions in lipid shells, rafts and related biomembrane domains. Cell Mol Life Sci 60: 1027–1032. doi: 10.1007/s00018-003-3003-1
[5]	Fantini J (2007) Interaction of proteins with lipid rafts through glycolipid-binding domains: Biochemical background and potential therapeutic applications. Curr Med Chem 14: 2911–2917. doi: 10.2174/092986707782360033
[6]	Sezgin E, Levental I, Mayor S, et al. (2017) The mystery of membrane organization: Composition, regulation and roles of lipid rafts. Nat Rev Mol Cell Biol 18: 361–374. doi: 10.1038/nrm.2017.16
[7]	Schutz GJ, Kada G, Pastushenko VP, et al. (2000) Properties of lipid microdomains in a muscle cell membrane visualized by single molecule microscopy. Emboj 19: 892–901. doi: 10.1093/emboj/19.5.892
[8]	Owen DM, Williamson DJ, Magenau A, et al. (2012) Sub-resolution lipid domains exist in the plasma membrane and regulate protein diffusion and distribution. Nat Commun 3: 1256. doi: 10.1038/ncomms2273
[9]	Fantini J, Barrantes FJ (2009) Sphingolipid/cholesterol regulation of neurotransmitter receptor conformation and function. Biochim Biophys Acta 1788: 2345–2361. doi: 10.1016/j.bbamem.2009.08.016
[10]	And DAB, London E (1998) Functions of lipid rafts in biological membranes. Annu Rev Cell Dev Biol 14: 111–136. doi: 10.1146/annurev.cellbio.14.1.111
[11]	Pike LJ (2006) Rafts defined: A report on the Keystone Symposium on lipid rafts and cell function. J Lipid Res 47: 1597–1598. doi: 10.1194/jlr.E600002-JLR200
[12]	Frisz JF, Klitzing HA, Lou K, et al. (2013) Sphingolipid domains in the plasma membranes of fibroblasts are not enriched with cholesterol. J Biol Chem 288: 16855–16861. doi: 10.1074/jbc.M113.473207
[13]	Frisz JF, Lou K, Klitzing HA, et al. (2013) Direct chemical evidence for sphingolipid domains in the plasma membranes of fibroblasts. Proc Natl Acad Sci U S A 110: E613–E622. doi: 10.1073/pnas.1216585110
[14]	Fantini J, Garmy N, Mahfoud R, et al. (2002) Lipid rafts: Structure, function and role in HIV, Alzheimer's and prion diseases. Expert Rev Mol Med 4: 1–22.
[15]	Fantini J, Barrantes FJ (2013) How cholesterol interacts with membrane proteins: An exploration of cholesterol-binding sites including CRAC, CARC, and tilted domains. Front Physiol 4: 31.
[16]	Battari AE, Ah-Kye E, Muller JM, et al. (1985) Modification of HT 29 cell response to the vasoactive intestinal peptide (VIP) by membrane fluidization. Biochimie 67: 1217–1223. doi: 10.1016/S0300-9084(85)80130-9
[17]	Merrill AH Jr (2011) Sphingolipid and glycosphingolipid metabolic pathways in the era of sphingolipidomics. Chem Rev 111: 6387–6422. doi: 10.1021/cr2002917
[18]	Westover EJ, Covey DF (2004) The enantiomer of cholesterol. J Membr Biol 202: 61–72. doi: 10.1007/s00232-004-0714-7
[19]	Mustafi D, Palczewski K (2009) Topology of class A G protein-coupled receptors: Insights gained from crystal structures of rhodopsins, adrenergic and adenosine receptors. Mol Pharmacol 75: 1–12. doi: 10.1124/mol.108.051938
[20]	Coleman JL, Ngo T, Smith NJ (2017) The G protein-coupled receptor N-terminus and receptor signalling: N-tering a new era. Cell Signalling 33: 1–9. doi: 10.1016/j.cellsig.2017.02.004
[21]	Topiol S, Sabio M (2009) X-ray structure breakthroughs in the GPCR transmembrane region. Biochem Pharmacol 78: 11–20. doi: 10.1016/j.bcp.2009.02.012
[22]	Jafurulla M, Tiwari S, Chattopadhyay A (2011) Identification of cholesterol recognition amino acid consensus (CRAC) motif in G-protein coupled receptors. Biochem Biophys Res Commun 404: 569–573. doi: 10.1016/j.bbrc.2010.12.031
[23]	Rasmussen SG, Choi HJ, Rosenbaum DM, et al. (2007) Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature 450: 383–387. doi: 10.1038/nature06325
[24]	Lu ZL, Saldanha JW, Hulme EC (2002) Seven-transmembrane receptors: Crystals clarify. Trends Pharmacol Sci 23: 140–146. doi: 10.1016/S0165-6147(00)01973-8
[25]	Russ WP, Engelman DM (2000) The GxxxG motif: A ramework for transmembrane helix-helix association. J Mol Biol 296: 911–919. doi: 10.1006/jmbi.1999.3489
[26]	Fantini J, Yahi N (2015) Brain lipids in synaptic function and neurological disease. Clues to innovative therapeutic strategies for brain disorders. Elsevier, New-York.
[27]	Stangl M, Schneider D (2015) Functional competition within a membrane: Lipid recognition vs. transmembrane helix oligomerization. Biochim Biophys Acta 1848: 1886–1896. doi: 10.1016/j.bbamem.2015.03.011
[28]	Hanson MA, Cherezov V, Griffith MT, et al. (2008) A specific cholesterol binding site is established by the 2.8 A structure of the human β2-adrenergic receptor. Structure 16: 897–905.
[29]	Paila YD, Chattopadhyay A (2010) Membrane cholesterol in the function and organization of G-protein coupled receptors. Springer Neth 51: 439–466.
[30]	Paila YD, Ganguly S, Chattopadhyay A (2010) Metabolic depletion of sphingolipids impairs ligand binding and signaling of human serotonin1A receptors. Biochemistry 49: 2389–2397. doi: 10.1021/bi1001536
[31]	Paila YD, Tiwari S, Chattopadhyay A (2009) Are specific nonannular cholesterol binding sites present in G-protein coupled receptors? Biochim Biophys Acta 1788: 295–302. doi: 10.1016/j.bbamem.2008.11.020
[32]	Audet M, Bouvier M (2012) Restructuring G-protein- coupled receptor activation. Cell 151: 14–23. doi: 10.1016/j.cell.2012.09.003
[33]	Luttrell LM (2006) Transmembrane signaling by G protein-coupled receptors. Methods Mol Biol 332: 3–49.
[34]	Pluhackova K, Gahbauer S, Kranz F, et al. (2016) Dynamic Cholesterol-Conditioned Dimerization of the G Protein Coupled Chemokine Receptor Type 4. PLoS Comput Biol 12: e1005169. doi: 10.1371/journal.pcbi.1005169
[35]	Gregory H, Taylor CL, Hopkins CR (1982) Luteinizing hormone release from dissociated pituitary cells by dimerization of occupied LHRH receptors. Nature 300: 269–271. doi: 10.1038/300269a0
[36]	Fantini J, Di Scala C, Baier CJ, et al. (2016) Molecular mechanisms of protein-cholesterol interactions in plasma membranes: Functional distinction between topological (tilted) and consensus (CARC/CRAC) domains. Chem Phys Lipids 199: 52–60. doi: 10.1016/j.chemphyslip.2016.02.009
[37]	Di Scala C, Fantini J (2017) Hybrid In Silico/In Vitro Approaches for the Identification of Functional Cholesterol-Binding Domains in Membrane Proteins. Methods Mol Biol 1583: 7–19. doi: 10.1007/978-1-4939-6875-6_2
[38]	Li H, Papadopoulos V (1998) Peripheral-type benzodiazepine receptor function in cholesterol transport. Identification of a putative cholesterol recognition/interaction amino acid sequence and consensus pattern. Endocrinology 139: 4991–4997.
[39]	Epand RF, Thomas A, Brasseur R, et al. (2006) Juxtamembrane protein segments that contribute to recruitment of cholesterol into domains. Biochemistry 45: 6105–6114. doi: 10.1021/bi060245+
[40]	Epand RM (2006) Cholesterol and the interaction of proteins with membrane domains. Prog Lipid Res 45: 279–294. doi: 10.1016/j.plipres.2006.02.001
[41]	Epand RM (2008) Proteins and cholesterol-rich domains. Biochim Biophys Acta 1778: 1576–1582. doi: 10.1016/j.bbamem.2008.03.016
[42]	Epand RM, Thomas A, Brasseur R, et al. (2010) Cholesterol interaction with proteins that partition into membrane domains: An overview. Subcell Biochem 51: 253–278. doi: 10.1007/978-90-481-8622-8_9
[43]	Baier CJ, Fantini J, Barrantes FJ (2011) Disclosure of cholesterol recognition motifs in transmembrane domains of the human nicotinic acetylcholine receptor. Sci Rep 1: 69. doi: 10.1038/srep00069
[44]	Di Scala C, Baier CJ, Evans LS, et al. (2017) Relevance of CARC and CRAC Cholesterol-Recognition Motifs in the Nicotinic Acetylcholine Receptor and Other Membrane-Bound Receptors. Curr Top Membr 80: 3–23. doi: 10.1016/bs.ctm.2017.05.001
[45]	Fantini J, Di Scala C, Evans LS, et al. (2016) A mirror code for protein-cholesterol interactions in the two leaflets of biological membranes. Sci Rep 6: 21907. doi: 10.1038/srep21907
[46]	Rosenhouse-Dantsker A, Noskov S, Durdagi S, et al. (2013) Identification of novel cholesterol-binding regions in Kir2 channels. J Biol Chem 288: 31154–31164. doi: 10.1074/jbc.M113.496117
[47]	Levitan I, Singh DK, Rosenhouse-Dantsker A (2014) Cholesterol binding to ion channels. Front Physiol 5: 65.
[48]	Nishio M, Umezawa Y, Fantini J, et al. (2014) CH-pi hydrogen bonds in biological macromolecules. Phys Chem Chem Phys 16: 12648–12683. doi: 10.1039/C4CP00099D
[49]	Barrantes FJ, Fantini J (2016) From hopanoids to cholesterol: Molecular clocks of pentameric ligand-gated ion channels. Prog Lipid Res 63: 1–13. doi: 10.1016/j.plipres.2016.03.003
[50]	Barbera N, Ayee MAA, Akpa BS, et al. (2017) Differential effects of sterols on ion channels: Stereospecific Binding vs Stereospecific Response. Curr Top Membr 80: 25–50. doi: 10.1016/bs.ctm.2017.06.001
[51]	Romanenko VG, Rothblat GH, Levitan I (2002) Modulation of endothelial inward-rectifier K⁺ current by optical isomers of cholesterol. Biophys J 83: 3211–3222. doi: 10.1016/S0006-3495(02)75323-X
[52]	Mannock DA, Lewis RNAH, Mcelhaney RN, et al. (2008) Comparative calorimetric and spectroscopic studies of the effects of cholesterol and epicholesterol on the thermotropic phase behaviour of dipalmitoylphosphatidylcholine bilayer membranes. Biochim Biophys Acta 1778: 2191–2202. doi: 10.1016/j.bbamem.2008.05.004
[53]	Bukiya AN, Osborn CV, Kuntamallappanavar G, et al. (2015) Cholesterol increases the open probability of cardiac KACh currents. Biochim Biophys Acta 1848: 2406–2413. doi: 10.1016/j.bbamem.2015.07.007
[54]	Song Y, Kenworthy AK, Sanders CR (2014) Cholesterol as a co-solvent and a ligand for membrane proteins. Protein Sci 23: 1–22. doi: 10.1002/pro.2599
[55]	Zhou X, Xu J (2012) Free cholesterol induces higher beta-sheet content in Abeta peptide oligomers by aromatic interaction with Phe19. PLoS One 7: e46245. doi: 10.1371/journal.pone.0046245
[56]	Beel AJ, Mobley CK, Kim HJ, et al. (2008) Structural studies of the transmembrane C-terminal domain of the amyloid precursor protein (APP): Does APP function as a cholesterol sensor? Biochemistry 47: 9428–9446. doi: 10.1021/bi800993c
[57]	Beel AJ, Sakakura M, Barrett PJ, et al. (2010) Direct binding of cholesterol to the amyloid precursor protein: An important interaction in lipid-Alzheimer's disease relationships? Biochim Biophys Acta 1801: 975–982. doi: 10.1016/j.bbalip.2010.03.008
[58]	Nadezhdin KD, Bocharova OV, Bocharov EV, et al. (2011) Structural and dynamic study of the transmembrane domain of the amyloid precursor protein. Acta Nat 3: 69–76.
[59]	Barrett PJ, Song Y, Van Horn WD, et al. (2012) The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol. Science 336: 1168–1171. doi: 10.1126/science.1219988
[60]	Di Scala C, Yahi N, Lelièvre C, et al. (2013) Biochemical identification of a linear cholesterol-binding domain within Alzheimer's β amyloid peptide. ACS Chem Neurosci 4: 509–517. doi: 10.1021/cn300203a
[61]	Palmer M (2004) Cholesterol and the activity of bacterial toxins. FEMS Microbiol Lett 238: 281–289. doi: 10.1111/j.1574-6968.2004.tb09768.x
[62]	Rohmer M, Bouvier P, Ourisson G (1979) Molecular evolution of biomembranes: Structural equivalents and phylogenetic precursors of sterols. Proc Natl Acad Sci U S A 76: 847–851. doi: 10.1073/pnas.76.2.847
[63]	Saenz JP, Grosser D, Bradley AS, et al. (2015) Hopanoids as functional analogues of cholesterol in bacterial membranes. Proc Natl Acad Sci U S A 112: 11971–11976. doi: 10.1073/pnas.1515607112
[64]	Arish M, Husein A, Kashif M, et al. (2015) Orchestration of membrane receptor signaling by membrane lipids. Biochimie 113: 111–124. doi: 10.1016/j.biochi.2015.04.005
[65]	Westover EJ, Covey DF, Brockman HL, et al. (2003) Cholesterol depletion results in site-specific increases in epidermal growth factor receptor phosphorylation due to membrane level effects. Studies with cholesterol enantiomers. J Biol Chem 278: 51125–51133.
[66]	Liu Y, Li R, Ladisch S (2004) Exogenous ganglioside GD1a enhances epidermal growth factor receptor binding and dimerization. J Biol Chem 279: 36481–36489. doi: 10.1074/jbc.M402880200
[67]	Goldkorn T, Dressler KA, Muindi J, et al. (1991) Ceramide stimulates epidermal growth factor receptor phosphorylation in A431 human epidermoid carcinoma cells. Evidence that ceramide may mediate sphingosine action. J Biol Chem 266: 16092–16097.
[68]	Alexander LD, Ding Y, Alagarsamy S, et al. (2006) Arachidonic acid induces ERK activation via Src SH2 domain association with the epidermal growth factor receptor. Kidney Int 69: 1823–1832. doi: 10.1038/sj.ki.5000363
[69]	Petiot A, Faure J, Stenmark H, et al. (2003) PI3P signaling regulates receptor sorting but not transport in the endosomal pathway. J Cell Biol 162: 971–979. doi: 10.1083/jcb.200303018
[70]	Singh P, Paila YD, Chattopadhyay A (2012) Role of glycosphingolipids in the function of human serotonin 1A receptors. J Neurochem 123: 716–724. doi: 10.1111/jnc.12008
[71]	Fernández Nievas GA, Barrantes FJ, Antollini SS (2008) Modulation of nicotinic acetylcholine receptor conformational state by free fatty acids and steroids. J Biol Chem 283: 21478–21486. doi: 10.1074/jbc.M800345200
[72]	Crain SM, Shen KF (1998) GM1 ganglioside-induced modulation of opioid receptor-mediated functions. Ann N Y Acad Sci 845: 106–125. doi: 10.1111/j.1749-6632.1998.tb09665.x
[73]	Mahfoud R, Garmy N, Maresca M, et al. (2002) Identification of a common sphingolipid-binding domain in Alzheimer, prion, and HIV-1 proteins. J Biol Chem 277: 11292–11296. doi: 10.1074/jbc.M111679200
[74]	Fantini J, Yahi N, Garmy N (2013) Cholesterol accelerates the binding of Alzheimer's β-amyloid peptide to ganglioside GM1 through a universal hydrogen-bond-dependent sterol tuning of glycolipid conformation. Front Physiol 4: 120.
[75]	Fantini J, Garmy N, Yahi N (2006) Prediction of glycolipid-binding domains from the amino acid sequence of lipid raft-associated proteins: Application to HpaA, a protein involved in the adhesion of Helicobacter pylori to gastrointestinal cells. Biochemistry 45: 10957–10962. doi: 10.1021/bi060762s
[76]	Fantini J, Yahi N (2011) Molecular basis for the glycosphingolipid-binding specificity of alpha-synuclein: key role of tyrosine 39 in membrane insertion. J Mol Biol 408: 654–669. doi: 10.1016/j.jmb.2011.03.009
[77]	Fantini J, Yahi N (2010) Molecular insights into amyloid regulation by membrane cholesterol and sphingolipids: Common mechanisms in neurodegenerative diseases. Expert Rev Mol Med 12: e27. doi: 10.1017/S1462399410001602
[78]	Levy M, Garmy N, Gazit E, et al. (2006) The minimal amyloid-forming fragment of the islet amyloid polypeptide is a glycolipid-binding domain. FEBS J 273: 5724–5735. doi: 10.1111/j.1742-4658.2006.05562.x
[79]	Taieb N, Maresca M, Guo XJ, et al. (2009) The first extracellular domain of the tumour stem cell marker CD133 contains an antigenic ganglioside-binding motif. Cancer Lett 278: 164–173. doi: 10.1016/j.canlet.2009.01.013
[80]	Chakrabandhu K, Huault S, Garmy N, et al. (2008) The extracellular glycosphingolipid-binding motif of Fas defines its internalization route, mode and outcome of signals upon activation by ligand. Cell Death Differ 15: 1824–1837. doi: 10.1038/cdd.2008.115
[81]	Di Scala C, Nouara Y, Sonia B, et al. (2016) Common molecular mechanism of amyloid pore formation by Alzheimer's β-amyloid peptide and α-synuclein. Sci Rep 6: 28781. doi: 10.1038/srep28781
[82]	Di Scala C, Yahi N, Flores A, et al. (2016) Broad neutralization of calcium-permeable amyloid pore channels with a chimeric Alzheimer/Parkinson peptide targeting brain gangliosides. Biochim Biophys Acta 1862: 213–222. doi: 10.1016/j.bbadis.2015.11.012
[83]	Di Scala C, Yahi N, Flores A, et al. (2016) Comparison of the amyloid pore forming properties of rat and human Alzheimer's beta-amyloid peptide 1–42: Calcium imaging data. Data Brief 6: 640–643. doi: 10.1016/j.dib.2016.01.019
[84]	Sarnataro D, Campana V, Paladino S, et al. (2004) PrPC association with lipid rafts in the early secretory pathway stabilizes its cellular conformation. Mol Biol Cell 15: 4031–4042. doi: 10.1091/mbc.E03-05-0271

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