Skip to main content

Cholesterol Interaction with Proteins That Partition into Membrane Domains: An Overview

  • Chapter
  • First Online:
Cholesterol Binding and Cholesterol Transport Proteins:

Part of the book series: Subcellular Biochemistry ((SCBI,volume 51))

Abstract

Biological membranes are complex structures composed largely of proteins and lipids. These components have very different structural and physical properties and consequently they do not form a single homogeneous mixture. Rather components of the mixture are more enriched in some regions than in others. This can be demonstrated with simple lipid mixtures that spontaneously segregate components so as to form different lipid phases that are immiscible with one another. The segregation of molecular components of biological membranes also involves proteins. One driving force that would promote the segregation of membrane components is the preferential interaction between a protein and certain lipid components. Among the varied lipid components of mammalian membranes, the structure and physical properties of cholesterol is quite different from that of other major membrane lipids. It would therefore be expected that in many cases proteins would have very different energies of interaction with cholesterol vs. those of other membrane lipids. This would be sufficient to cause segregation of components in membranes. The factors that facilitate the interaction of proteins with cholesterol are varied and are not yet completely understood. However, there are certain groups that are present in some proteins that facilitate interaction of the protein with cholesterol. These groups include saturated acyl chains of lipidated proteins, as well as certain amino acid sequences. Although there is some understanding as to why these particular groups favour interaction with cholesterol, our knowledge of these molecular features is not sufficiently developed to allow for the design of agents that will modify such binding.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adams, C. M., Reitz, J., De Brabander, J. K., Feramisco, J. D., Li, L., Brown, M. S., and Goldstein, J. L., 2004, Cholesterol and 25-hydroxycholesterol inhibit activation of SREBPs by different mechanisms, both involving SCAP and Insigs. J. Biol. Chem. 279: 52772–52780.

    CAS  PubMed  Google Scholar 

  • Aloia, R. C., Tian, H., and Jensen, F. C., 1993, Lipid composition and fluidity of the human immunodeficiency virus envelope and host cell plasma membranes. Proc. Natl. Acad. Sci. USA 90: 5181–5185.

    CAS  PubMed  Google Scholar 

  • Anikovsky, M., Dale, L., Ferguson, S., and Petersen, N., 2008, Resonance energy transfer in cells: a new look at fixation effect and receptor aggregation on cell membrane. Biophys. J. 95: 1349–1359.

    CAS  PubMed  Google Scholar 

  • Apellaniz, B., Nir, S., and Nieva, J. L., 2009, Distinct mechanisms of lipid bilayer perturbation induced by peptides derived from the membrane-proximal external region of HIV-1 gp41. Biochemistry 48: 5320–5331.

    CAS  PubMed  Google Scholar 

  • Boesze-Battaglia, K., Besack, D., McKay, T., Zekavat, A., Otis, L., Jordan-Sciutto, K., and Shenker, B. J., 2006, Cholesterol-rich membrane microdomains mediate cell cycle arrest induced by Actinobacillus actinomycetemcomitans cytolethal-distending toxin. Cell Microbiol. 8: 823–836.

    CAS  PubMed  Google Scholar 

  • Boesze-Battaglia, K., Brown, A., Walker, L., Besack, D., Zekavat, A., Wrenn, S., Krummenacher, C., and Shenker, B. J., 2009, Cytolethal distending toxin-induced cell cycle arrest of lymphocytes is dependent upon recognition and binding to cholesterol. J. Biol. Chem. 284: 10650–10658.

    CAS  PubMed  Google Scholar 

  • Brasseur, R., 1995, Simulating the folding of small proteins by use of the local minimum energy and the free solvation energy yields native-like structures. J. Mol. Graph. 13: 312–322.

    CAS  PubMed  Google Scholar 

  • Brown, A. J., Sun, L., Feramisco, J. D., Brown, M. S., and Goldstein, J. L., 2002, Cholesterol addition to ER membranes alters conformation of SCAP, the SREBP escort protein that regulates cholesterol metabolism. Mol. Cell 10: 237–245.

    CAS  PubMed  Google Scholar 

  • Brown, D. A. and London, E., 2000, Structure and function of sphingolipid- and cholesterol-rich membrane rafts. J. Biol. Chem. 275: 17221–17224.

    CAS  PubMed  Google Scholar 

  • Brown, D. A. and Rose, J. K., 1992, Sorting of GPI-anchored proteins to glycolipid-enriched membrane subdomains during transport to the apical cell surface. Cell 68: 533–544.

    CAS  PubMed  Google Scholar 

  • Brugger, B., Glass, B., Haberkant, P., Leibrecht, I., Wieland, F. T., and Krausslich, H. G., 2006, The HIV lipidome: a raft with an unusual composition. Proc. Natl. Acad. Sci. USA 103: 2641–2646.

    PubMed  Google Scholar 

  • Chakrabandhu, K., Herincs, Z., Huault, S., Dost, B., Peng, L., Conchonaud, F., Marguet, D., He, H. T., and Hueber, A. O., 2007, Palmitoylation is required for efficient Fas cell death signaling. EMBO J. 26: 209–220.

    CAS  PubMed  Google Scholar 

  • Chen, S. S. L., Yang, P., Ke, P. Y., Li, H. F., Chan, W. E., Chang, D. K., Chuang, C. K., Tsai, Y., and Huang, S. C., 2009, 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. 83: 870–883.

    CAS  PubMed  Google Scholar 

  • Conrath, K. E., Wernery, U., Muyldermans, S., and Nguyen, V. K., 2003, Emergence and evolution of functional heavy-chain antibodies in Camelidae. Dev. Comp. Immunol. 27: 87–103.

    CAS  PubMed  Google Scholar 

  • Crane, J. M., Kiessling, V., and Tamm, L. K., 2005, Measuring lipid asymmetry in planar supported bilayers by fluorescence interference contrast microscopy. Langmuir 21: 1377–1388.

    CAS  PubMed  Google Scholar 

  • de Almeida, R. F., Loura, L. M., and Prieto, M., 2009, Membrane lipid domains and rafts: current applications of fluorescence lifetime spectroscopy and imaging. Chem. Phys. Lipids 157: 61–77.

    PubMed  Google Scholar 

  • Del Real, G., Jimenez-Baranda, S., Lacalle, R. A., Mira, E., Lucas, P., Gomez-Mouton, C., Carrera, A. C., Martinez, A., and Manes, S., 2002, Blocking of HIV-1 infection by targeting CD4 to nonraft membrane domains. J. Exp. Med. 196: 293–301.

    CAS  PubMed  Google Scholar 

  • Dietrich, C., Bagatolli, L. A., Volovyk, Z. N., Thompson, N. L., Levi, M., Jacobson, K., and Gratton, E., 2001, Lipid rafts reconstituted in model membranes. Biophys. J. 80: 1417–1428.

    CAS  PubMed  Google Scholar 

  • Dietrich, C., Yang, B., Fujiwara, T., Kusumi, A., and Jacobson, K., 2002, Relationship of lipid rafts to transient confinement zones detected by single particle tracking. Biophys. J. 82: 274–284.

    CAS  PubMed  Google Scholar 

  • Douglass, A. D. and Vale, R. D., 2005, Single-molecule microscopy reveals plasma membrane microdomains created by protein-protein networks that exclude or trap signaling molecules in T cells. Cell 121: 937–950.

    CAS  PubMed  Google Scholar 

  • Drbal, K., Moertelmaier, M., Holzhauser, C., Muhammad, A., Fuertbauer, E., Howorka, S., Hinterberger, M., Stockinger, H., and Schutz, G. J., 2007, Single-molecule microscopy reveals heterogeneous dynamics of lipid raft components upon TCR engagement. Int. J. Immunol. 19: 675–684.

    CAS  Google Scholar 

  • Eggeling, C., Ringemann, C., Medda, R., Schwarzmann, G., Sandhoff, K., Polyakova, S., Belov, V. N., Hein, B., von, M. C., Schonle, A., and Hell, S. W., 2009, Direct observation of the nanoscale dynamics of membrane lipids in a living cell. Nature 457: 1159–1162.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Epand, R. F., Thomas, A., Brasseur, R., Vishwanathan, S. A., Hunter, E., and Epand, R. M., 2006, Juxtamembrane protein segments that contribute to recruitment of cholesterol into domains. Biochemistry 45: 6105–6114.

    CAS  PubMed  Google Scholar 

  • Epand, R. M., 2006, Cholesterol and the interaction of proteins with membrane domains. Prog. Lipid Res. 45: 279–294.

    CAS  PubMed  Google Scholar 

  • Epand, R. M., Epand, R. F., Sayer, B. G., Melacini, G., Palgulachari, M. N., Segrest, J. P., and Anantharamaiah, G. M., 2004, An apolipoprotein AI mimetic peptide: membrane interactions and the role of cholesterol. Biochemistry 43: 5073–5083.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Fujita, M. and Jigami, Y., 2008, Lipid remodeling of GPI-anchored proteins and its function. Biochim. Biophys. Acta 1780: 410–420.

    CAS  PubMed  Google Scholar 

  • Goldstein, J. L., Bose-Boyd, R. A., and Brown, M. S., 2006, Protein sensors for membrane sterols. Cell 124: 35–46.

    CAS  PubMed  Google Scholar 

  • Graham, D. R., Chertova, E., Hilburn, J. M., Arthur, L. O., and Hildreth, J. E., 2003, Cholesterol depletion of human immunodeficiency virus type 1 and simian immunodeficiency virus with beta-cyclodextrin inactivates and permeabilizes the virions: evidence for virion-associated lipid rafts. J. Virol. 77: 8237–8248.

    CAS  PubMed  Google Scholar 

  • Guyader, M., Kiyokawa, E., Abrami, L., Turelli, P., and Trono, D., 2002, Role for human immunodeficiency virus type 1 membrane cholesterol in viral internalization. J. Virol. 76: 10356–10364.

    CAS  PubMed  Google Scholar 

  • Harder, T., Scheiffele, P., Verkade, P., and Simons, K., 1998, Lipid domain structure of the plasma membrane revealed by patching of membrane components. J. Cell Biol. 141: 929–942.

    CAS  PubMed  Google Scholar 

  • Harris, J., Werling, D., Hope, J. C., Taylor, G., and Howard, C. J., 2002, Caveolae and caveolin in immune cells: distribution and functions. Trends Immunol. 23: 158–164.

    CAS  PubMed  Google Scholar 

  • Hayashi, M., Shimada, Y., Inomata, M., and Ohno-Iwashita, Y., 2006, Detection of cholesterol-rich microdomains in the inner leaflet of the plasma membrane. Biochem. Biophys. Res. Commun. 351: 713–718.

    CAS  PubMed  Google Scholar 

  • Heerklotz, H., 2002, Triton promotes domain formation in lipid raft mixtures. Biophys. J. 83: 2693–2701.

    CAS  PubMed  Google Scholar 

  • Herreros, J., Ng, T., and Schiavo, G., 2001, Lipid rafts act as specialized domains for tetanus toxin binding and internalization into neurons. Mol. Biol. Cell 12: 2947–2960.

    CAS  PubMed  Google Scholar 

  • Hofman, E. G., Ruonala, M. O., Bader, A. N., van den, H. D., Voortman, J., Roovers, R. C., Verkleij, A. J., Gerritsen, H. C., and van Bergen En Henegouwen PM, 2008, EGF induces coalescence of different lipid rafts. J. Cell Sci. 121: 2519–2528.

    CAS  PubMed  Google Scholar 

  • Honerkamp-Smith, A. R., Veatch, S. L., and Keller, S. L., 2009, An introduction to critical points for biophysicists; observations of compositional heterogeneity in lipid membranes. Biochim. Biophys. Acta 1788: 53–63.

    CAS  PubMed  Google Scholar 

  • Houjou, T., Hayakawa, J., Watanabe, R., Tashima, Y., Maeda, Y., Kinoshita, T., and Taguchi, R., 2007, Changes in molecular species profiles of glycosylphosphatidylinositol anchor precursors in early stages of biosynthesis. J. Lipid Res. 48: 1599–1606.

    CAS  PubMed  Google Scholar 

  • Huarte, N., Lorizate, M., Maeso, R., Kunert, R., Arranz, R., Valpuesta, J. M., and Nieva, J. L., 2008a, The broadly neutralizing anti-HIV-1 4E10 monoclonal antibody is better adapted to membrane-bound epitope recognition and blocking than 2F5. J. Virol. 82: 8986–8996.

    CAS  PubMed  Google Scholar 

  • Huarte, N., Lorizate, M., Kunert, R., and Nieva, J. L., 2008b, Lipid modulation of membrane-bound epitope recognition and blocking by HIV-1 neutralizing antibodies. FEBS Lett. 582: 3798–3804.

    CAS  PubMed  Google Scholar 

  • Hug, P., Lin, H. M., Korte, T., Xiao, X., Dimitrov, D. S., Wang, J. M., Puri, A., and Blumenthal, R., 2000, Glycosphingolipids promote entry of a broad range of human immunodeficiency virus type 1 isolates into cell lines expressing CD4, CXCR4, and/or CCR5. J. Virol. 74: 6377–6385.

    CAS  PubMed  Google Scholar 

  • Ipsen, J. H., Karlstrom, G., Mouritsen, O. G., Wennerstrom, H., and Zuckermann, M. J., 1987, Phase equilibria in the phosphatidylcholine-cholesterol system. Biochim. Biophys. Acta 905: 162–172.

    CAS  PubMed  Google Scholar 

  • Jamin, N., Neumann, J. M., Ostuni, M. A., Vu, T. K., Yao, Z. X., Murail, S., Robert, J. C., Giatzakis, C., Papadopoulos, V., and Lacapere, J. J., 2005, Characterization of the cholesterol recognition amino acid consensus sequence of the peripheral-type benzodiazepine receptor. Mol. Endocrinol. 19: 588–594.

    CAS  PubMed  Google Scholar 

  • Karpen, H. E., Bukowski, J. T., Hughes, T., Gratton, J. P., Sessa, W. C., and Gailani, M. R., 2001, The sonic hedgehog receptor patched associates with caveolin-1 in cholesterol-rich microdomains of the plasma membrane. J. Biol. Chem. 276: 19503–19511.

    CAS  PubMed  Google Scholar 

  • Kiessling, V. and Tamm, L. K., 2003, Measuring distances in supported bilayers by fluorescence interference-contrast microscopy: polymer supports and SNARE proteins. Biophys. J. 84: 408–418.

    CAS  PubMed  Google Scholar 

  • Kiessling, V., Wan, C., and Tamm, L. K., 2009, Domain coupling in asymmetric lipid bilayers. Biochim. Biophys. Acta 1788: 64–71.

    CAS  PubMed  Google Scholar 

  • Kinoshita, T., Fujita, M., and Maeda, Y., 2008, Biosynthesis, remodelling and functions of mammalian GPI-anchored proteins: recent progress. J. Biochem. (Tokyo) 144: 287–294.

    CAS  Google Scholar 

  • Kusumi, A. and Suzuki, K., 2005, Toward understanding the dynamics of membrane-raft-based molecular interactions. Biochim. Biophys. Acta 1746: 234–251.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Langhorst, M. F., Solis, G. P., Hannbeck, S., Plattner, H., and Stuermer, C. A., 2007, Linking membrane microdomains to the cytoskeleton: regulation of the lateral mobility of reggie-1/flotillin-2 by interaction with actin. FEBS Lett. 581: 4697–4703.

    CAS  PubMed  Google Scholar 

  • Leung, K., Kim, J. O., Ganesh, L., Kabat, J., Schwartz, O., and Nabel, G. J., 2008, HIV-1 assembly: viral glycoproteins segregate quantally to lipid rafts that associate individually with HIV-1 capsids and virions. Cell Host. Microbe. 3: 285–292.

    CAS  PubMed  Google Scholar 

  • Levine, T., 2004, SSD: sterol-sensing direct. Dev. Cell. 7: 152–153.

    CAS  PubMed  Google Scholar 

  • Li, H. and 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.

    CAS  PubMed  Google Scholar 

  • Liao, Z., Cimakasky, L. M., Hampton, R., Nguyen, D. H., and Hildreth, J. E., 2001, Lipid rafts and HIV pathogenesis: host membrane cholesterol is required for infection by HIV type 1. AIDS Res. Hum. Retroviruses 17: 1009–1019.

    CAS  PubMed  Google Scholar 

  • Liao, Z., Graham, D. R., and Hildreth, J. E., 2003, Lipid rafts and HIV pathogenesis: virion-associated cholesterol is required for fusion and infection of susceptible cells. AIDS. Res. Hum. Retroviruses 19: 675–687.

    CAS  PubMed  Google Scholar 

  • Lichtenberg, D., Goñi, F. M., and Heerklotz, H., 2005, Detergent-resistant membranes should not be identified with membrane rafts. Trends Biochem. Sci. 30: 430–436.

    CAS  PubMed  Google Scholar 

  • Lin, X., Derdeyn, C. A., Blumenthal, R., West, J., and Hunter, E., 2003, Progressive truncations C terminal to the membrane-spanning domain of simian immunodeficiency virus Env reduce fusogenicity and increase concentration dependence of Env for fusion. J. Virol. 77: 7067–7077.

    CAS  PubMed  Google Scholar 

  • Lingwood, D., Ries, J., Schwille, P., and Simons, K., 2008, Plasma membranes are poised for activation of raft phase coalescence at physiological temperature. Proc. Natl. Acad. Sci USA 105: 10005–10010.

    CAS  PubMed  Google Scholar 

  • Lins, L., Thomas, A., and Brasseur, R., 2003, Analysis of accessible surface of residues in proteins. Protein Sci. 12: 1406–1417.

    CAS  PubMed  Google Scholar 

  • Lorizate, M., Cruz, A., Huarte, N., Kunert, R., Perez-Gil, J., and Nieva, J. L., 2006, Recognition and blocking of HIV-1 gp41 pre-transmembrane sequence by monoclonal 4E10 antibody in a raft-like membrane environment. J. Biol. Chem. 281: 39598–39606.

    CAS  PubMed  Google Scholar 

  • Lorizate, M., Huarte, N., Saez-Cirion, A., and Nieva, J. L., 2008, Interfacial pre-transmembrane domains in viral proteins promoting membrane fusion and fission. Biochim. Biophys. Acta 1778: 1624–1639.

    CAS  PubMed  Google Scholar 

  • Loura, L. M., de Almeida, R. F., Silva, L. C., and Prieto, M., 2009, FRET analysis of domain formation and properties in complex membrane systems. Biochim. Biophys. Acta 1788: 209–224.

    CAS  PubMed  Google Scholar 

  • Luo, C., Wang, K., Liu, d. Q., Li, Y., and Zhao, Q. S., 2008, The functional roles of lipid rafts in T cell activation, immune diseases and HIV infection and prevention. Cell. Mol. Immunol. 5: 1–7.

    CAS  PubMed  Google Scholar 

  • Luo, X., Sharma, D., Inouye, H., Lee, D., Avila, R. L., Salmona, M., and Kirschner, D. A., 2007, Cytoplasmic domain of human myelin protein zero likely folded as beta-structure in compact myelin. Biophys. J. 92: 1585–1597.

    CAS  PubMed  Google Scholar 

  • Maeda, Y., Tashima, Y., Houjou, T., Fujita, M., Yoko-o T, Jigami, Y., Taguchi, R., and Kinoshita, T., 2007, Fatty acid remodeling of GPI-anchored proteins is required for their raft association. Mol. Biol. Cell 18: 1497–1506.

    CAS  PubMed  Google Scholar 

  • McConville, M. J. and Ferguson, M. A., 1993, The structure, biosynthesis and function of glycosylated phosphatidylinositols in the parasitic protozoa and higher eukaryotes. Biochem. J. 294 (Pt 2): 305–324.

    CAS  PubMed  Google Scholar 

  • Melkonian, K. A., Ostermeyer, A. G., Chen, J. Z., Roth, M. G., and Brown, D. A., 1999, Role of lipid modifications in targeting proteins to detergent-resistant membrane rafts. Many raft proteins are acylated, while few are prenylated. J. Biol. Chem. 274: 3910–3917.

    CAS  PubMed  Google Scholar 

  • Meyer, B. H., Segura, J. M., Martinez, K. L., Hovius, R., George, N., Johnsson, K., and Vogel, H., 2006, FRET imaging reveals that functional neurokinin-1 receptors are monomeric and reside in membrane microdomains of live cells. Proc. Natl. Acad. Sci USA 103: 2138–2143.

    CAS  PubMed  Google Scholar 

  • Milhiet, P. E., Giocondi, M. C., and Le Grimellec, C., 2002, Cholesterol is not crucial for the existence of microdomains in kidney brush-border membrane models. J. Biol. Chem. 277: 875–878.

    CAS  PubMed  Google Scholar 

  • Morandat, S., Bortolato, M., and Roux, B., 2002, Cholesterol-dependent insertion of glycosylphosphatidylinositol-anchored enzyme. Biochim. Biophys. Acta 1564: 473–478.

    CAS  PubMed  Google Scholar 

  • Munoz-Barroso, I., Salzwedel, K., Hunter, E., and Blumenthal, R., 1999, Role of the membrane-proximal domain in the initial stages of human immunodeficiency virus type 1 envelope glycoprotein-mediated membrane fusion. J. Virol. 73: 6089–6092.

    CAS  PubMed  Google Scholar 

  • Palmer, M., 2004, Cholesterol and the activity of bacterial toxins. FEMS Microbiol. Lett. 238: 281–289.

    CAS  PubMed  Google Scholar 

  • Parton, R. G. and Simons, K., 2007, The multiple faces of caveolae. Nat. Rev. Mol. Cell Biol. 8: 185–194.

    CAS  PubMed  Google Scholar 

  • Pike, L. J., 2006, Rafts defined: a report on the Keystone Symposium on Lipid Rafts and Cell Function. J Lipid Res. 47: 1597–1598.

    CAS  PubMed  Google Scholar 

  • Popik, W., Alce, T. M., and Au, W. C., 2002, Human immunodeficiency virus type 1 uses lipid raft-colocalized CD4 and chemokine receptors for productive entry into CD4(+) T cells. J. Virol. 76: 4709–4722.

    CAS  PubMed  Google Scholar 

  • Pralle, A., Keller, P., Florin, E. L., Simons, K., and Horber, J. K., 2000, Sphingolipid-cholesterol rafts diffuse as small entities in the plasma membrane of mammalian cells. J. Cell Biol. 148: 997–1008.

    CAS  PubMed  Google Scholar 

  • Radhakrishnan, A., Goldstein, J. L., McDonald, J. G., and Brown, M. S., 2008, Switch-like control of SREBP-2 transport triggered by small changes in ER cholesterol: a delicate balance. Cell Metab. 8: 512–521.

    CAS  PubMed  Google Scholar 

  • Radhakrishnan, A. and McConnell, H. M., 2000, Chemical activity of cholesterol in membranes. Biochemistry 39: 8119–8124.

    CAS  PubMed  Google Scholar 

  • Radhakrishnan, A., Sun, L. P., Kwon, H. J., Brown, M. S., and Goldstein, J. L., 2004, Direct binding of cholesterol to the purified membrane region of SCAP: mechanism for a sterol-sensing domain. Mol. Cell. 15: 259–268.

    CAS  PubMed  Google Scholar 

  • Rawat, S. S., Eaton, J., Gallo, S. A., Martin, T. D., Ablan, S., Ratnayake, S., Viard, M., KewalRamani, V. N., Wang, J. M., Blumenthal, R., and Puri, A., 2004, Functional expression of CD4, CXCR4, and CCR5 in glycosphingolipid-deficient mouse melanoma GM95 cells and susceptibility to HIV-1 envelope glycoprotein-triggered membrane fusion. Virology 318: 55–65.

    CAS  PubMed  Google Scholar 

  • Redman, C. A., Thomas-Oates, J. E., Ogata, S., Ikehara, Y., and Ferguson, M. A., 1994, Structure of the glycosylphosphatidylinositol membrane anchor of human placental alkaline phosphatase. Biochem. J. 302 (Pt 3): 861–865.

    CAS  PubMed  Google Scholar 

  • Resh, M. D., 2004, Membrane targeting of lipid modified signal transduction proteins. Subcell. Biochem. 37: 217–232.

    CAS  PubMed  Google Scholar 

  • Resh, M. D., 2006, Palmitoylation of ligands, receptors, and intracellular signaling molecules. Sci. STKE 2006: re14.

    PubMed  Google Scholar 

  • Risselada, H. J. and Marrink, S. J., 2008, The molecular face of lipid rafts in model membranes. Proc. Natl. Acad. Sci USA 105: 17367–17372.

    CAS  PubMed  Google Scholar 

  • Roberts, W. L., Myher, J. J., Kuksis, A., Low, M. G., and Rosenberry, T. L., 1988, Lipid analysis of the glycoinositol phospholipid membrane anchor of human erythrocyte acetylcholinesterase. Palmitoylation of inositol results in resistance to phosphatidylinositol-specific phospholipase C. J. Biol. Chem. 263: 18766–18775.

    CAS  PubMed  Google Scholar 

  • Rudd, P. M., Morgan, B. P., Wormald, M. R., Harvey, D. J., van den Berg, C. W., Davis, S. J., Ferguson, M. A., and Dwek, R. A., 1997, The glycosylation of the complement regulatory protein, human erythrocyte CD59. J. Biol. Chem. 272: 7229–7244.

    CAS  PubMed  Google Scholar 

  • Saez-Cirion, A., Arrondo, J. L., Gomara, M. J., Lorizate, M., Iloro, I., Melikyan, G., and Nieva, J. L., 2003, Structural and functional roles of HIV-1 gp41 pretransmembrane sequence segmentation. Biophys. J. 85: 3769–3780.

    CAS  PubMed  Google Scholar 

  • Saez-Cirion, A., Nir, S., Lorizate, M., Agirre, A., Cruz, A., Perez-Gil, J., and Nieva, J. L., 2002, Sphingomyelin and cholesterol promote HIV-1 gp41 pretransmembrane sequence surface aggregation and membrane restructuring. J. Biol. Chem. 277: 21776–21785.

    CAS  PubMed  Google Scholar 

  • Saher, G., Quintes, S., Mobius, W., Wehr, M. C., Kramer-Albers, E. M., Brugger, B., and Nave, K. A., 2009, Cholesterol regulates the endoplasmic reticulum exit of the major membrane protein P0 required for peripheral myelin compaction. J. Neurosci. 29: 6094–6104.

    CAS  PubMed  Google Scholar 

  • Salzwedel, K., West, J. T., and Hunter, E., 1999, A conserved tryptophan-rich motif in the membrane-proximal region of the human immunodeficiency virus type 1 gp41 ectodomain is important for Env-mediated fusion and virus infectivity. J. Virol. 73: 2469–2480.

    CAS  PubMed  Google Scholar 

  • Sarin, P. S., Gallo, R. C., Scheer, D. I., Crews, F., and Lippa, A. S., 1985, Effects of a novel compound (AL 721) on HTLV-III infectivity in vitro. N. Engl. J. Med. 313: 1289–1290.

    CAS  PubMed  Google Scholar 

  • Schaffner, C. P., Plescia, O. J., Pontani, D., Sun, D., Thornton, A., Pandey, R. C., and Sarin, P. S., 1986, Anti-viral activity of amphotericin B methyl ester: inhibition of HTLV-III replication in cell culture. Biochem. Pharmacol. 35: 4110–4113.

    CAS  PubMed  Google Scholar 

  • Schutz, G. J., Kada, G., Pastushenko, V. P., and Schindler, H., 2000, Properties of lipid microdomains in a muscle cell membrane visualized by single molecule microscopy. EMBO J. 19: 892–901.

    CAS  PubMed  Google Scholar 

  • Scolari, S., Engel, S., Krebs, N., Plazzo, A. P., De Almeida, R. F. M., Prieto, M., Veit, M., and Herrmann, A., 2009, Lateral distribution of the transmembrane domain of influenza virus hemagglutinin revealed by time-resolved fluorescence imaging. J. Biol. Chem. 284: 15708–15716.

    CAS  PubMed  Google Scholar 

  • Sharma, P., Varma, R., Sarasij, R. C., Ira, Gousset, K., Krishnamoorthy, G., Rao, M., and Mayor, S., 2004, Nanoscale organization of multiple GPI-anchored proteins in living cell membranes. Cell 116: 577–589.

    CAS  PubMed  Google Scholar 

  • Sharom, F. J. and Lehto, M. T., 2002, Glycosylphosphatidylinositol-anchored proteins: structure, function, and cleavage by phosphatidylinositol-specific phospholipase C. Biochem. Cell Biol. 80: 535–549.

    CAS  PubMed  Google Scholar 

  • Shenker, B. J., Besack, D., McKay, T., Pankoski, L., Zekavat, A., and Demuth, D. R., 2005, Induction of cell cycle arrest in lymphocytes by Actinobacillus actinomycetemcomitans cytolethal distending toxin requires three subunits for maximum activity. J. Immunol. 174: 2228–2234.

    CAS  PubMed  Google Scholar 

  • Shnaper, S., Sackett, K., Gallo, S. A., Blumenthal, R., and Shai, Y., 2004, The C- and the N-terminal regions of glycoprotein 41 ectodomain fuse membranes enriched and not enriched with cholesterol, respectively. J. Biol. Chem. 279: 18526–18534.

    CAS  PubMed  Google Scholar 

  • Simons, K. and Ikonen, E., 1997, Functional rafts in cell membranes. Nature 387: 569–572.

    CAS  PubMed  Google Scholar 

  • Simons, K. and Toomre, D., 2000, Lipid rafts and signal transduction. Nat. Rev. Mol. Cell Biol. 1: 31–39.

    CAS  PubMed  Google Scholar 

  • Soni, S. P., LoCascio, D. S., Liu, Y., Williams, J. A., Bittman, R., Stillwell, W., and Wassall, S. R., 2008, Docosahexaenoic acid enhances segregation of lipids between raft and nonraft domains: 2H-NMR study. Biophys. J. 95: 203–214.

    CAS  PubMed  Google Scholar 

  • Stockl, M., Plazzo, A. P., Korte, T., and Herrmann, A., 2008, Detection of lipid domains in model and cell membranes by fluorescence lifetime imaging microscopy of fluorescent lipid analogues. J. Biol. Chem. 283: 30828–30837.

    PubMed  Google Scholar 

  • Suarez, T., Nir, S., Goni, F. M., Saez-Cirion, A., and Nieva, J. L., 2000, The pre-transmembrane region of the human immunodeficiency virus type-1 glycoprotein: a novel fusogenic sequence. FEBS Lett. 477: 145–149.

    CAS  PubMed  Google Scholar 

  • Sun, L. P., Li, L., Goldstein, J. L., and Brown, M. S., 2005, Insig required for sterol-mediated inhibition of Scap/SREBP binding to COPII proteins in vitro. J. Biol. Chem. 280: 26483–26490.

    CAS  PubMed  Google Scholar 

  • Sun, Z. Y., Oh, K. J., Kim, M., Yu, J., Brusic, V., Song, L., Qiao, Z., Wang, J. H., Wagner, G., and Reinherz, E. L., 2008, HIV-1 broadly neutralizing antibody extracts its epitope from a kinked gp41 ectodomain region on the viral membrane. Immunity 28: 52–63.

    PubMed  Google Scholar 

  • Thomas, A., Deshayes, S., Decaffmeyer, M., Van Eyck, M. H., Charloteaux, B., and Brasseur, R., 2006, Prediction of peptide structure: how far are we? Proteins 65: 889–897.

    CAS  PubMed  Google Scholar 

  • Thomas, A., Milon, A., and Brasseur, R., 2004, Partial atomic charges of amino acids in proteins. Proteins 56: 102–109.

    CAS  PubMed  Google Scholar 

  • Ueda, Y., Yamaguchi, R., Ikawa, M., Okabe, M., Morii, E., Maeda, Y., and Kinoshita, T., 2007, PGAP1 knock-out mice show otocephaly and male infertility. J. Biol. Chem. 282: 30373–30380.

    CAS  PubMed  Google Scholar 

  • Veatch, S. L. and Keller, S. L., 2005a, Miscibility phase diagrams of giant vesicles containing sphingomyelin. Phys. Rev. Lett. 94: 148101.

    PubMed  Google Scholar 

  • Veatch, S. L. and Keller, S. L., 2005b, Seeing spots: Complex phase behavior in simple membranes. Biochim. Biophys. Acta Mol. Cell Res. 1746: 172–185.

    CAS  Google Scholar 

  • Veatch, S. L., Polozov, I. V., Gawrisch, K., and Keller, S. L., 2004, Liquid domains in vesicles investigated by NMR and fluorescence microscopy. Biophys. J. 86: 2910–2922.

    CAS  PubMed  Google Scholar 

  • Viard, M., Parolini, I., Rawat, S. S., Fecchi, K., Sargiacomo, M., Puri, A., and Blumenthal, R., 2004, The role of glycosphingolipids in HIV signaling, entry and pathogenesis. Glycoconj. J. 20: 213–222.

    CAS  PubMed  Google Scholar 

  • Viard, M., Parolini, I., Sargiacomo, M., Fecchi, K., Ramoni, C., Ablan, S., Ruscetti, F. W., Wang, J. M., and Blumenthal, R., 2002, Role of cholesterol in human immunodeficiency virus type 1 envelope protein-mediated fusion with host cells. J. Virol. 76: 11584–11595.

    CAS  PubMed  Google Scholar 

  • Vincent, N., Genin, C., and Malvoisin, E., 2002, Identification of a conserved domain of the HIV-1 transmembrane protein gp41 which interacts with cholesteryl groups. Biochim. Biophys. Acta 1567: 157–164.

    CAS  PubMed  Google Scholar 

  • Vishwanathan, S. A. and Hunter, E., 2008, Importance of the membrane-perturbing properties of the membrane-proximal external region of human immunodeficiency virus type 1 gp41 to viral fusion. J. Virol. 82: 5118–5126.

    CAS  PubMed  Google Scholar 

  • Vishwanathan, S. A., Thomas, A., Brasseur, R., Epand, R. F., Hunter, E., and Epand, R. M., 2008a, Hydrophobic substitutions in the first residue of the CRAC segment of the gp41 protein of HIV. Biochemistry 47: 124–130.

    CAS  PubMed  Google Scholar 

  • Vishwanathan, S. A., Thomas, A., Brasseur, R., Epand, R. F., Hunter, E., and Epand, R. M., 2008b, Large changes in the CRAC segment of gp41 of HIV do not destroy fusion activity if the segment interacts with cholesterol. Biochemistry. 47: 11869–11876.

    Google Scholar 

  • von Arnim, C. A., Kinoshita, A., Peltan, I. D., Tangredi, M. M., Herl, L., Lee, B. M., Spoelgen, R., Hshieh, T. T., Ranganathan, S., Battey, F. D., Liu, C. X., Bacskai, B. J., Sever, S., Irizarry, M. C., Strickland, D. K., and Hyman, B. T., 2005, The low density lipoprotein receptor-related protein (LRP) is a novel beta-secretase (BACE1) substrate. J. Biol. Chem. 280: 17777–17785.

    Google Scholar 

  • Wagner, M. L. and Tamm, L. K., 2000, Tethered polymer-supported planar lipid bilayers for reconstitution of integral membrane proteins: silane-polyethyleneglycol-lipid as a cushion and covalent linker. Biophys. J. 79: 1400–1414.

    CAS  PubMed  Google Scholar 

  • Wan, C., Kiessling, V., and Tamm, L. K., 2008, Coupling of cholesterol-rich lipid phases in asymmetric bilayers. Biochemistry 47: 2190–2198.

    CAS  PubMed  Google Scholar 

  • Wang, J., Gunning, W., Kelley, K. M., and Ratnam, M., 2002, Evidence for segregation of heterologous GPI-anchored proteins into separate lipid rafts within the plasma membrane. J. Membr. Biol. 189: 35–43.

    CAS  PubMed  Google Scholar 

  • Yabe, D., Xia, Z. P., Adams, C. M., and Rawson, R. B., 2002, Three mutations in sterol-sensing domain of SCAP block interaction with insig and render SREBP cleavage insensitive to sterols. Proc. Natl. Acad. Sci. USA 99: 16672–16677.

    CAS  PubMed  Google Scholar 

  • Yang, T., Espenshade, P. J., Wright, M. E., Yabe, D., Gong, Y., Aebersold, R., Goldstein, J. L., and Brown, M. S., 2002, Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell 110: 489–500.

    CAS  PubMed  Google Scholar 

  • Yethiraj, A. and Weisshaar, J. C., 2007, Why are lipid rafts not observed in vivo? Biophys. J. 93: 3113–3119.

    CAS  PubMed  Google Scholar 

  • Zanetti, G., Briggs, J. A., Grunewald, K., Sattentau, Q. J., and Fuller, S. D., 2006, Cryo-electron tomographic structure of an immunodeficiency virus envelope complex in situ. PLoS Pathog. 2: e83.

    PubMed  Google Scholar 

  • Zhu, P., Liu, J., Bess, J., Jr., Chertova, E., Lifson, J. D., Grise, H., Ofek, G. A., Taylor, K. A., and Roux, K. H., 2006, Distribution and three-dimensional structure of AIDS virus envelope spikes. Nature 441: 847–852.

    CAS  PubMed  Google Scholar 

  • Zuckermann, M. J., Ipsen, J. H., Miao, L., Mouritsen, O. G., Nielsen, M., Polson, J., Thewalt, J., Vattulainen, I., and Zhu, H., 2004, Modeling lipid-sterol bilayers: applications to structural evolution, lateral diffusion, and rafts. Meth. Enzymol 383: 198–229.

    CAS  PubMed  Google Scholar 

  • Zwick, M. B., Jensen, R., Church, S., Wang, M., Stiegler, G., Kunert, R., Katinger, H., and Burton, D. R., 2005, Anti-human immunodeficiency virus type 1 (HIV-1) antibodies 2F5 and 4E10 require surprisingly few crucial residues in the membrane-proximal external region of glycoprotein gp41 to neutralize HIV-1. J. Virol. 79: 1252–1261.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Richard M. Epand .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Epand, R.M., Thomas, A., Brasseur, R., Epand, R.F. (2010). Cholesterol Interaction with Proteins That Partition into Membrane Domains: An Overview. In: Harris, J. (eds) Cholesterol Binding and Cholesterol Transport Proteins:. Subcellular Biochemistry, vol 51. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-8622-8_9

Download citation

Publish with us

Policies and ethics