T. Kimura, W. Jennings, and R. M. Epand, Roles of specific lipid species in the cell and their molecular mechanism, Prog Lipid Res, vol.62, pp.75-92, 2016.

J. Fantini, N. Garmy, R. Mahfoud, and N. Yahi, Alzheimer's and prion diseases, Lipid rafts: structure, function and role in HIV, vol.4, pp.1-22, 2002.

S. T. Yang, A. Kreutzberger, J. Lee, V. Kiessling, and L. K. Tamm, The role of cholesterol in membrane fusion, Chem Phys Lipids, vol.199, pp.136-143, 2016.

V. Howe, L. J. Sharpe, S. J. Alexopoulos, S. V. Kunze, N. K. Chua et al., Cholesterol homeostasis: How do cells sense sterol excess, Chem Phys Lipids, vol.199, pp.170-178, 2016.

M. Jafurulla and A. Chattopadhyay, Structural Stringency of Cholesterol for Membrane Protein Function Utilizing Stereoisomers as Novel Tools: A Review, Cholesterol Homeostasis: Methods and Protocols, vol.2017, pp.21-39

R. M. Epand, S. D. Rychnovsky, J. D. Belani, and R. F. Epand, Role of chirality in peptide-induced formation of cholesterol-rich domains, Biochem J, vol.390, pp.541-548, 2005.

A. J. Sodt, M. L. Sandar, K. Gawrisch, R. W. Pastor, and E. Lyman, The molecular structure of the liquidordered phase of lipid bilayers, J Am Chem Soc, vol.136, pp.725-732, 2014.

D. L. Gater, O. Saurel, I. Iordanov, W. Liu, V. Cherezov et al., Two classes of cholesterol binding sites for the beta2AR revealed by thermostability and NMR, Biophys J, vol.107, pp.2305-2312, 2014.

E. Rouviere, C. Arnarez, L. Yang, and E. Lyman, Identification of Two New Cholesterol Interaction Sites on the A2A Adenosine Receptor, Biophys J, vol.113, pp.2415-2424, 2017.

E. Byrne, R. Sircar, P. S. Miller, G. Hedger, G. Luchetti et al., Structural basis of Smoothened regulation by its extracellular domains, Nature, vol.535, pp.517-522, 2016.

I. M. Posada, J. Fantini, F. X. Contreras, F. Barrantes, A. Alonso et al., A cholesterol recognition motif in human phospholipid scramblase 1, Biophys J, vol.107, pp.1383-1392, 2014.

J. Fantini, D. Scala, C. Baier, C. J. Barrantes, and F. J. , Molecular mechanisms of protein-cholesterol interactions in plasma membranes: Functional distinction between topological (tilted) and consensus (CARC/CRAC) domains, Chem Phys Lipids, vol.199, pp.52-60, 2016.

J. Fantini and F. J. Barrantes, How cholesterol interacts with membrane proteins: an exploration of cholesterol-binding sites including CRAC, CARC, and tilted domains, Front Physiol, vol.4, p.31, 2013.

A. Rosenhouse-dantsker, S. Noskov, S. Durdagi, D. E. Logothetis, and I. Levitan, Identification of novel cholesterol-binding regions in Kir2 channels, J Biol Chem, vol.288, pp.31154-31164, 2013.

M. A. Hanson, V. Cherezov, M. T. Griffith, C. B. Roth, V. P. Jaakola et al., A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor, Structure, vol.16, pp.897-905, 2008.

J. Fantini, D. Scala, C. Evans, L. S. Williamson, P. T. Barrantes et al., A mirror code for proteincholesterol interactions in the two leaflets of biological membranes, Sci Rep, vol.6, p.21907, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01772916

L. Jaremko, M. Jaremko, K. Giller, S. Becker, and M. Zweckstetter, Structure of the mitochondrial translocator protein in complex with a diagnostic ligand, Science, vol.343, pp.1363-1366, 2014.

H. Li and V. Papadopoulos, Peripheral-type benzodiazepine receptor function in cholesterol transport. Identification of a putative cholesterol recognition/interaction amino acid sequence and consensus pattern, Endocrinology, vol.139, pp.4991-4997, 1998.

C. J. Baier, J. Fantini, and F. J. Barrantes, Disclosure of cholesterol recognition motifs in transmembrane domains of the human nicotinic acetylcholine receptor, Sci Rep, vol.1, p.69, 2011.

M. Palmer, Cholesterol and the activity of bacterial toxins, FEMS Microbiol Lett, vol.238, pp.281-289, 2004.

M. Nishio, Y. Umezawa, J. Fantini, M. S. Weiss, and P. Chakrabarti, CH-pi hydrogen bonds in biological macromolecules, Phys Chem Chem Phys, vol.16, pp.12648-12683, 2014.

A. G. Lee, Lipid-protein interactions in biological membranes: a structural perspective, Biochim Biophys Acta, vol.1612, pp.1-40, 2003.

J. Fantini and N. Yahi, Brain Lipids in Synaptic Function and Neurological Disease. Clues to Innovative Therapeutic Strategies for Brain Disorders, 2015.

J. Fantini and F. J. Barrantes, How membrane lipids control the 3D structure and function of receptors, AIMS Biophysics, vol.5, pp.22-35, 2018.

S. P. Pydi, M. Jafurulla, L. Wai, R. P. Bhullar, P. Chelikani et al., Cholesterol modulates bitter taste receptor function, Biochim Biophys Acta, vol.1858, pp.2081-2087, 2016.

L. J. Sharpe, G. Rao, P. M. Jones, E. Glancey, S. M. Aleidi et al., Cholesterol sensing by the ABCG1 lipid transporter: Requirement of a CRAC motif in the final transmembrane domain, Biochim Biophys Acta, vol.1851, pp.956-964, 2015.

L. E. Robinson, M. Shridar, P. Smith, and R. D. Murrell-lagnado, Plasma membrane cholesterol as a regulator of human and rodent P2X7 receptor activation and sensitization, J Biol Chem, vol.289, pp.31983-31994, 2014.

A. K. Singh, J. Mcmillan, A. N. Bukiya, B. Burton, A. L. Parrill et al., Multiple cholesterol recognition/interaction amino acid consensus (CRAC) motifs in cytosolic C tail of Slo1 subunit determine cholesterol sensitivity of Ca2+-and voltage-gated K+ (BK) channels, J Biol Chem, vol.287, pp.20509-20521, 2012.

N. Jamin, J. M. Neumann, M. A. Ostuni, T. K. Vu, Z. X. Yao et al., Characterization of the cholesterol recognition amino acid consensus sequence of the peripheral-type benzodiazepine receptor, Mol Endocrinol, vol.19, pp.588-594, 2005.

R. M. Epand, Cholesterol and the interaction of proteins with membrane domains, Prog Lipid Res, vol.45, pp.279-294, 2006.

R. F. Epand, A. Thomas, R. Brasseur, S. A. Vishwanathan, E. Hunter et al., Juxtamembrane protein segments that contribute to recruitment of cholesterol into domains, Biochemistry, vol.45, pp.6105-6114, 2006.

M. B. Ulmschneider and M. S. Sansom, Amino acid distributions in integral membrane protein structures, Biochim Biophys Acta, vol.1512, pp.1-14, 2001.

M. Ferraro, M. Masetti, M. Recanatini, A. Cavalli, and G. Bottegoni, Mapping Cholesterol Interaction Sites on Serotonin Transporter through Coarse-Grained Molecular Dynamics, PLoS One, vol.11, p.166196, 2016.

G. A. Morrill, A. B. Kostellow, and R. K. Gupta, The role of receptor topology in the vitamin D3 uptake and Ca(2+) response systems, Biochem Biophys Res Commun, vol.477, pp.834-840, 2016.

G. A. Morrill, A. B. Kostellow, and R. K. Gupta, Computational analysis of the extracellular domain of the Ca(2)(+)-sensing receptor: an alternate model for the Ca(2)(+) sensing region, Biochem Biophys Res Commun, vol.459, pp.36-41, 2015.

D. Marsh and F. J. Barrantes, Immobilized lipid in acetylcholine receptor-rich membranes from Torpedo marmorata, Proc Natl Acad Sci U S A, vol.75, pp.4329-4333, 1978.

F. J. Barrantes, Structural basis for lipid modulation of nicotinic acetylcholine receptor function, Brain Res Brain Res Rev, vol.47, pp.71-95, 2004.

Y. Song, A. K. Kenworthy, and C. R. Sanders, Cholesterol as a co-solvent and a ligand for membrane proteins, Protein Sci, vol.23, pp.1-22, 2014.

J. L. Goldstein, R. A. Debose-boyd, and M. S. Brown, Protein sensors for membrane sterols, Cell, vol.124, pp.35-46, 2006.

P. E. Kuwabara and M. Labouesse, The sterol-sensing domain: multiple families, a unique role, Trends Genet, vol.18, pp.193-201, 2002.

J. L. Goldstein and M. S. Brown, Regulation of the mevalonate pathway, Nature, vol.343, pp.425-430, 1990.

J. E. Carette, M. Raaben, A. C. Wong, A. S. Herbert, G. Obernosterer et al., Ebola virus entry requires the cholesterol transporter Niemann-Pick C1, vol.477, pp.340-343, 2011.

M. Cote, J. Misasi, T. Ren, A. Bruchez, K. Lee et al., Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection, Nature, vol.477, pp.344-348, 2011.

A. Gay, D. Rye, and A. Radhakrishnan, Switch-like responses of two cholesterol sensors do not require protein oligomerization in membranes, Biophys J, vol.108, pp.1459-1469, 2015.

M. Motamed, Y. Zhang, M. L. Wang, J. Seemann, H. J. Kwon et al., Identification of luminal Loop 1 of Scap protein as the sterol sensor that maintains cholesterol homeostasis, J Biol Chem, vol.286, pp.18002-18012, 2011.

Y. Gao, Y. Zhou, J. L. Goldstein, M. S. Brown, and A. Radhakrishnan, Cholesterol-induced conformational changes in the sterol-sensing domain of the Scap protein suggest feedback mechanism to control cholesterol synthesis, J Biol Chem, vol.292, pp.8729-8737, 2017.

C. M. Adams, J. Reitz, D. Brabander, J. K. Feramisco, J. D. Li et al., Cholesterol and 25-hydroxycholesterol inhibit activation of SREBPs by different mechanisms, both involving SCAP and Insigs, J Biol Chem, vol.279, pp.52772-52780, 2004.

R. E. Infante, L. Abi-mosleh, A. Radhakrishnan, J. D. Dale, M. S. Brown et al., Purified NPC1 protein. I. Binding of cholesterol and oxysterols to a 1278-amino acid membrane protein, J Biol Chem, vol.283, pp.1052-1063, 2008.

R. E. Infante, A. Radhakrishnan, L. Abi-mosleh, L. N. Kinch, M. L. Wang et al., Purified NPC1 protein: II. Localization of sterol binding to a 240-amino acid soluble luminal loop, J Biol Chem, vol.283, pp.1064-1075, 2008.

X. Li, F. Lu, M. N. Trinh, P. Schmiege, J. Seemann et al., 3.3 A structure of Niemann-Pick C1 protein reveals insights into the function of the C-terminal luminal domain in cholesterol transport, Proc Natl Acad Sci, vol.114, pp.9116-9121, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01975196

X. Li, J. Wang, E. Coutavas, H. Shi, Q. Hao et al., Structure of human Niemann-Pick C1 protein, Proc Natl Acad Sci, vol.113, pp.8212-8217, 2016.

H. J. Kwon, L. Abi-mosleh, M. L. Wang, J. Deisenhofer, J. L. Goldstein et al., Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol, Cell, vol.137, pp.1213-1224, 2009.

X. Gong, H. Qian, X. Zhou, J. Wu, T. Wan et al., Structural Insights into the Niemann-Pick C1 (NPC1)-Mediated Cholesterol Transfer and Ebola Infection, vol.165, pp.1467-1478, 2016.

N. Sever, B. L. Song, D. Yabe, J. L. Goldstein, M. S. Brown et al., Insig-dependent ubiquitination and degradation of mammalian 3-hydroxy-3-methylglutaryl-CoA reductase stimulated by sterols and geranylgeraniol, J Biol Chem, vol.278, pp.52479-52490, 2003.

N. K. Chua, V. Howe, N. Jatana, L. Thukral, and A. J. Brown, A conserved degron containing an amphipathic helix regulates the cholesterol-mediated turnover of human squalene monooxygenase, a rate-limiting enzyme in cholesterol synthesis, J Biol Chem, vol.292, pp.19959-19973, 2017.

A. D. Albert, J. E. Young, and P. L. Yeagle, Rhodopsin-cholesterol interactions in bovine rod outer segment disk membranes, Biochim Biophys Acta, vol.1285, pp.47-55, 1996.

G. Gimpl, K. Burger, and F. Fahrenholz, Cholesterol as modulator of receptor function, Biochemistry, vol.36, pp.10959-10974, 1997.

T. J. Pucadyil, S. Shrivastava, and A. Chattopadhyay, Membrane cholesterol oxidation inhibits ligand binding function of hippocampal serotonin(1A) receptors, Biochem Biophys Res Commun, vol.331, pp.422-427, 2005.

M. Caffrey, A comprehensive review of the lipid cubic phase or in meso method for crystallizing membrane and soluble proteins and complexes, Acta Crystallogr F Struct Biol Commun, vol.71, pp.3-18, 2015.

M. Caffrey, D. Li, and A. Dukkipati, Membrane protein structure determination using crystallography and lipidic mesophases: recent advances and successes, Biochemistry, vol.51, pp.6266-6288, 2012.

Y. D. Paila and A. Chattopadhyay, Membrane cholesterol in the function and organization of Gprotein coupled receptors, Subcell Biochem, vol.51, pp.439-466, 2010.

T. Hua, K. Vemuri, S. P. Nikas, R. B. Laprairie, Y. Wu et al., Crystal structures of agonist-bound human cannabinoid receptor CB1, Nature, vol.547, pp.468-471, 2017.

G. Gimpl, Interaction of G protein coupled receptors and cholesterol, Chem Phys Lipids, vol.199, pp.61-73, 2016.

Y. D. Paila, S. Tiwari, and A. Chattopadhyay, Are specific nonannular cholesterol binding sites present in G-protein coupled receptors?, Biochim Biophys Acta, vol.1788, pp.295-302, 2009.

O. B. Clarke and J. M. Gulbis, Oligomerization at the membrane: potassium channel structure and function, Adv Exp Med Biol, vol.747, pp.122-136, 2012.

I. Levitan, Y. Fang, A. Rosenhouse-dantsker, and V. Romanenko, Cholesterol and ion channels, Subcell Biochem, vol.51, pp.509-549, 2010.

A. Rosenhouse-dantsker, S. Noskov, D. E. Logothetis, and I. Levitan, Cholesterol sensitivity of KIR2.1 depends on functional inter-links between the N and C termini, Channels (Austin), vol.7, pp.303-312, 2013.

N. Barbera, M. Ayee, B. S. Akpa, and I. Levitan, Differential Effects of Sterols on Ion Channels: Stereospecific Binding vs Stereospecific Response. Curr Top Membr, vol.80, pp.25-50, 2017.

G. H. Addona, H. Sandermann, J. Kloczewiak, M. A. Husain, S. S. Miller et al., Where does cholesterol act during activation of the nicotinic acetylcholine receptor?, Biochim Biophys Acta, vol.1370, pp.299-309, 1998.

A. N. Bukiya, C. V. Osborn, G. Kuntamallappanavar, P. T. Toth, L. Baki et al., Rosenhouse-Dantsker A: Cholesterol increases the open probability of cardiac KACh currents, Biochim Biophys Acta, vol.1848, pp.2406-2413, 2015.

D. Scala, C. Chahinian, H. Yahi, N. Garmy, N. Fantini et al., Interaction of Alzheimer's beta-amyloid peptides with cholesterol: mechanistic insights into amyloid pore formation, Biochemistry, vol.53, pp.4489-4502, 2014.

D. Scala, C. Troadec, J. D. Lelievre, C. Garmy, N. Fantini et al., Mechanism of cholesterol-assisted oligomeric channel formation by a short Alzheimer beta-amyloid peptide, J Neurochem, vol.128, pp.186-195, 2014.

G. B. Irvine, O. M. El-agnaf, G. M. Shankar, and D. M. Walsh, Protein aggregation in the brain: the molecular basis for Alzheimer's and Parkinson's diseases, Mol Med, vol.14, pp.451-464, 2008.

R. S. Harrison, P. C. Sharpe, Y. Singh, and D. P. Fairlie, Amyloid peptides and proteins in review, Rev Physiol Biochem Pharmacol, vol.159, pp.1-77, 2007.

T. J. Esparza, H. Zhao, J. R. Cirrito, N. J. Cairns, R. J. Bateman et al., Amyloid-beta oligomerization in Alzheimer dementia versus high-pathology controls, Ann Neurol, vol.73, pp.104-119, 2013.

A. Quist, I. Doudevski, H. Lin, R. Azimova, D. Ng et al., Amyloid ion channels: a common structural link for protein-misfolding disease, Proc Natl Acad Sci, vol.102, pp.10427-10432, 2005.

H. Jang, L. Connelly, F. T. Arce, S. Ramachandran, R. Lal et al., Alzheimer's disease: which type of amyloid-preventing drug agents to employ?, Phys Chem Chem Phys, vol.15, pp.8868-8877, 2013.

D. Scala, C. Yahi, N. Boutemeur, S. Flores, A. Rodriguez et al., Common molecular mechanism of amyloid pore formation by Alzheimer's beta-amyloid peptide and alpha-synuclein, Sci Rep, vol.6, p.28781, 2016.

N. Yahi and J. Fantini, Deciphering the glycolipid code of Alzheimer's and Parkinson's amyloid proteins allowed the creation of a universal ganglioside-binding peptide, PLoS One, vol.9, p.104751, 2014.

J. Fantini, D. Carlus, and N. Yahi, The fusogenic tilted peptide (67-78) of alpha-synuclein is a cholesterol binding domain, Biochim Biophys Acta, vol.1808, pp.2343-2351, 2011.

B. Charloteaux, A. Lorin, R. Brasseur, and L. Lins, The "Tilted Peptide Theory" links membrane insertion properties and fusogenicity of viral fusion peptides, Protein Pept Lett, vol.16, pp.718-725, 2009.

I. D. Kerr, A. J. Haider, and I. C. Gelissen, The ABCG family of membrane-associated transporters: you don't have to be big to be mighty, Br J Pharmacol, vol.164, pp.1767-1779, 2011.

C. Vedhachalam, P. T. Duong, M. Nickel, D. Nguyen, P. Dhanasekaran et al., Mechanism of ATP-binding cassette transporter A1-mediated cellular lipid efflux to apolipoprotein A-I and formation of high density lipoprotein particles, J Biol Chem, vol.282, pp.25123-25130, 2007.

J. Neumann, D. Rose-sperling, and U. A. Hellmich, Diverse relations between ABC transporters and lipids: An overview, Biochim Biophys Acta, vol.1859, pp.605-618, 2017.

K. M. Mendez-acevedo, V. J. Valdes, A. Asanov, and L. Vaca, A novel family of mammalian transmembrane proteins involved in cholesterol transport, Sci Rep, vol.7, p.7450, 2017.

H. J. Risselada, Membrane Fusion Stalks and Lipid Rafts: A Love-Hate Relationship, vol.112, pp.2475-2478, 2017.

C. Enrich, C. Rentero, A. Hierro, and T. Grewal, Role of cholesterol in SNARE-mediated trafficking on intracellular membranes, J Cell Sci, vol.128, pp.1071-1081, 2015.

C. R. Wasser, M. Ertunc, X. Liu, and E. T. Kavalali, Cholesterol-dependent balance between evoked and spontaneous synaptic vesicle recycling, J Physiol, vol.579, pp.413-429, 2007.

A. Linetti, A. Fratangeli, E. Taverna, P. Valnegri, M. Francolini et al., Cholesterol reduction impairs exocytosis of synaptic vesicles, J Cell Sci, vol.123, pp.595-605, 2010.

M. Hao and J. S. Bogan, Cholesterol regulates glucose-stimulated insulin secretion through phosphatidylinositol 4,5-bisphosphate, J Biol Chem, vol.284, pp.29489-29498, 2009.

S. Koseoglu, S. A. Love, and C. L. Haynes, Cholesterol effects on vesicle pools in chromaffin cells revealed by carbon-fiber microelectrode amperometry, Anal Bioanal Chem, vol.400, pp.2963-2971, 2011.

J. Zhang, R. Xue, W. Y. Ong, and P. Chen, Roles of cholesterol in vesicle fusion and motion, Biophys J, vol.97, pp.1371-1380, 2009.

M. A. Churchward, T. Rogasevskaia, D. M. Brandman, H. Khosravani, P. Nava et al., Specific lipids supply critical negative spontaneous curvature--an essential component of native Ca2+-triggered membrane fusion, Biophys J, vol.94, pp.3976-3986, 2008.

M. A. Churchward, T. Rogasevskaia, J. Hofgen, J. Bau, and J. R. Coorssen, Cholesterol facilitates the native mechanism of Ca2+-triggered membrane fusion, J Cell Sci, vol.118, pp.4833-4848, 2005.

S. Manes, G. Del-real, and A. C. Martinez, Pathogens: raft hijackers, Nat Rev Immunol, vol.3, pp.557-568, 2003.

S. T. Yang, V. Kiessling, J. A. Simmons, J. M. White, and L. K. Tamm, HIV gp41-mediated membrane fusion occurs at edges of cholesterol-rich lipid domains, Nat Chem Biol, vol.11, pp.424-431, 2015.

P. Scheiffele, M. G. Roth, and K. Simons, Interaction of influenza virus haemagglutinin with sphingolipid-cholesterol membrane domains via its transmembrane domain, Embo j, vol.16, pp.5501-5508, 1997.

E. O. Freed, HIV-1 assembly, release and maturation, Nat Rev Microbiol, vol.13, pp.484-496, 2015.

J. Lee, D. A. Nyenhuis, E. A. Nelson, D. S. Cafiso, J. M. White et al., Structure of the Ebola virus envelope protein MPER/TM domain and its interaction with the fusion loop explains their fusion activity, Proc Natl Acad Sci, vol.114, pp.7987-7996, 2017.

P. J. Barrett, Y. Song, W. D. Van-horn, E. J. Hustedt, J. M. Schafer et al., The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol, Science, vol.336, pp.1168-1171, 2012.

Y. A. Klug, E. Rotem, R. Schwarzer, and Y. Shai, Mapping out the intricate relationship of the HIV envelope protein and the membrane environment, Biochim Biophys Acta, vol.1859, pp.550-560, 2017.

R. M. Epand, B. G. Sayer, and R. F. Epand, Peptide-induced formation of cholesterol-rich domains, Biochemistry, vol.42, pp.14677-14689, 2003.

R. F. Epand, B. G. Sayer, and R. M. Epand, The tryptophan-rich region of HIV gp41 and the promotion of cholesterol-rich domains, Biochemistry, vol.44, pp.5525-5531, 2005.

S. A. Vishwanathan, A. Thomas, R. Brasseur, R. F. Epand, E. Hunter et al., Large changes in the CRAC segment of gp41 of HIV do not destroy fusion activity if the segment interacts with cholesterol, Biochemistry, vol.47, pp.11869-11876, 2008.

S. A. Vishwanathan, A. Thomas, R. Brasseur, R. F. Epand, E. Hunter et al., Hydrophobic substitutions in the first residue of the CRAC segment of the gp41 protein of HIV, Biochemistry, vol.47, pp.124-130, 2008.

A. I. Greenwood, J. Pan, T. T. Mills, J. F. Nagle, R. M. Epand et al., CRAC motif peptide of the HIV-1 gp41 protein thins SOPC membranes and interacts with cholesterol, Biochim Biophys Acta, vol.1778, pp.1120-1130, 2008.

P. Carravilla, A. Cruz, I. Martin-ugarte, I. R. Oar-arteta, J. Torralba et al., Effects of HIV-1 gp41-Derived Virucidal Peptides on Virus-like Lipid Membranes, Biophys J, vol.113, pp.1301-1310, 2017.

S. S. Chen, P. Yang, P. Y. Ke, H. F. Li, W. E. Chan et al., Identification of the LWYIK motif located in the human immunodeficiency virus type 1 transmembrane gp41 protein as a distinct determinant for viral infection, J Virol, vol.83, pp.870-883, 2009.

, Figure Legends Figure 1. Geometry of the CRAC/cholesterol complex. The motif is oriented in the N-ter (top) to C-ter (bottom) direction. It displays three distinct zones (apolar in blue, aromatic in yellow

, Two cholesterol molecules bound to the human b2 adrenergic receptor (retrieved from PDB file # 3D4S)