Abstract
The importance of the surrounding lipid environment on the availability of glycolipid carbohydrate for ligand binding was demonstrated by studying the influence of phosphatidylcholine fatty acid chain length on binding of verotoxins (VT1 and VT2c) to their specific cell surface receptor, globotriaosylceramide (Gb3) in the presence of auxiliary lipids both in a microtitre plate surface bilayer film and in a liposome membrane model system. In the microtitre assay, both VT1 and VT2c binding to Gb3 was increased as a function of decreasing PC acyl chain length likely resulting in increased Gb3 exposure. In the liposome assay VT1 binding was similarly modulated, however the effect on VT2c binding was more complex and did not follow a simple function of increased carbohydrate exposure. Earlier work established that C22:1 and C18:1Gb3 fatty acid homologues were the preferred Gb3 receptor isoforms in the microtitre assay for VT1 and VT2c respectively. This selectivity was maintained in C16PC containing liposomes, but in C14PC liposomes, binding to C22:1Gb3 (but not C18:1Gb3) was elevated such that this Gb3 species now became the preferred receptor for both toxins. This change in verotoxin/Gb3 homologue binding selectivity in the presence of C14PC did not occur in the microtitre bilayer format. These results are consistent with our proposal that these toxins recognize different epitopes on the Gb3 oligosaccharide. We infer that relative availability of these epitopes for toxin binding in an artificial bilayer is influenced not only by the exposure due to the discrepancy between the fatty acyl chain lengths of Gb3 and PC, but by the physical mode of presentation of the bilayer structure. Such acyl chain length differences have a more marked effect in a supported bilayer film whereas only the largest discrepancies affect Gb3 receptor function in liposomes. The basis of phospholipid modulation of glycolipid carbohydrate accessibility for receptor function is likely complex and will involve phase separation, gel/liquid crystalline transition, packing and lateral mobility within the bilayer, suggesting that such parameters should be considered in the assessment of glycolipid receptor function in cells.
Similar content being viewed by others
References
O'Brien AD, Holmes RK (1987)Microbiol Rev 51: 206–20.
Konowalchuk J, Dickie N, Stavric S, Speirs JI (1978)Infect Immunol 20: 575–77.
Karmali MA (1989)Clin Microbiol Rev 2: 15–38.
Ramotar K, Boyd B, Tyrrell G, Gariepy J, Lingwood CA, Brunton J (1990)Biochem J 272: 805–11.
Head S, Karmali M, Lingwood CA (1991)J Biol Chem 266: 3617–21.
Riley LW, Remis RS, Helgerson SD, McGee HB, Wells JG, Davis BR, Hebert RJ, Olcott ES, Johnson LM, Hargrett NT, Blake PA, Cohen MC (1983)N Engl J Med 308: 681–85.
Dickie N, Speirs JI, Akhtar M, Johnson WM, Szabo RA (1989)J Clin Microbiol 27: 1973–78.
Karmali MA, Petric M, Lim C, Fleming PC, Arbus GS, Lior H (1985)J Infect Dis 151: 775–82.
Obrig TG, Vecchio PJD, Brown JE, Moran TP, Rowland BM, Judge TK, Rothman SW (1988)Infect Immun 56: 2373–78.
Obrig T, Louise C, Lingwood C, Boyd B, Barley-Maloney L, Daniel T (1993)J Biol Chem 268: 15484–88.
Lingwood CA, Law H, Richardson S, Petric M, Brunton JL, DeGrandis S, Karmali M (1987)J Biol Chem 262: 8834–39.
Waddell T, Head S, Petric M, Cohen A, Lingwood CA (1988)Biochem Biophys Res Commun 152: 674–79.
Waddell T, Cohen A, Lingwood CA (1990)Proc Natl Acad Sci USA 87: 7898–901.
Boyd B, Tyrrell G, Maloney M, Gyles C, Brunton J, Lingwood C (1993)J Exp Med 177: 1745–53.
Zoja J, Corna D, Farina C, Sacchi G, Lingwood C, Doyles M, Padhye V, Abbate M, Remuzzi G (1992)J Lab Clin Med 120: 229–38.
Pellizzari A, Pang H, Lingwood CA (1992)Biochem 31: 1363–70.
Kiarash A, Boyd B, Lingwood CA (1994)J Biol Chem 269: 11138–46.
Boyd B, Zhiuyan Z, Magnusson G, Lingwood CA (1994)Eur J Biochem 223: 873–78.
Sandvig K, Prydz K, Ryd M, van Deurs B (1991)J Cell Biol 113: 553–62.
Khine AA, Lingwood CA (1994)J Cell Physiol 161: 319–32.
Sandvig K, Garred O, Prydz K, Kozlov J, Hansen S, van Deurs B (1992)Nature 358: 510–12.
Sandvig K, Ryd M, Garred O, Schweda E, Holm PK (1994)J Cell Biol 126: 53–64.
Igarashi K, Ogasawara T, Ito K, Yutsudo T, Takeda Y (1987)FEMS Microbiol Letts 44: 91–94.
Mangeney M, Lingwood CA, Caillou B, Taga S, Tursz T, Wiels J (1993)Cancer Res 53: 5314–19.
Cohen A, Madrid-Marina V, Estrov Z, Freedman M, Lingwood CA, Dosch H-M (1990)Int Immunol 2: 1–8.
Alving CR, Urban KA, Richards RL (1980)Biochem Biophys Acta 600: 117–25.
Kannagi R, Nudelman E, Hakomori S (1982)Proc Natl Acad Sci USA 79: 3470–74.
Kannagi R, Stroup R, Cochran NA, Urdal DL, Young Jr WW, Hakomori S-I (1983)Cancer Res 43: 4997–5005.
Crook SJ, Boggs JM, Vistnes AI, Koshy KM (1986)Biochem 25: 7488–94.
Stewart RJ, Boggs J (1990)Biochemistry 29: 3644–53.
Stewart RJ, Boggs JM (1993)Biochemistry 32: 5605–14.
Myers M, Wortman C, Freire E (1984)Biochemistry 23: 1442–48.
Nyholm P-G, Pascher I (1993)Biochemistry 32: 1225–34.
Nyholm P-G, Pascher I (1993)Int J Biol Macromol 15: 43–51.
Basta M, Karmali M, Lingwood C (1989)J Clin Microbiol 127: 1617–22.
Huang A, DeGrandis S, Friesen J, Karmali MA, Petric M, Congi R, Brunton JL (1986)J Bacteriol 166: 375–79.
Hii JH, Gyles C, Morooka T, Karmali MA, Clarke R, DeGrandis S, Brunton JL (1991)J Clin Microbiol 29: 2704–9.
Yiu SCK, Lingwood CA (1992)Anal Biochem 202: 188–92.
Hope MJ, Bally MB, Webb G, Cullis PR (1985)Biochim Biophys Acta 812: 55–65.
Maggio B, Albert J, Yu R (1988)Biochim Biophys Acta 945: 145–60.
Jacewicz M, Clausen H, Nudelman E, Donohue-Rolfe A, Keusch GT (1986)J Exp Med 163: 1391–404.
Lindberg AA, Brown JE, Strömberg N, Westling-Ryd M, Schultz JE, Karlsson K-A (1987)J Biol Chem 262: 1779–85.
Head S, Ramotar K, Lingwood CA (1990)Infect Immun 58: 1532–37.
Kiarash A, Boyd B, Lingwood CA (1994) InRecent Advances in Verocytotoxin-Producing Eshcerichia Coli Infections, (Karmali MA, Goglio AG; eds) pp. 175–187, Amsterdam, Elsevier.
Nyholm P-G, Brunton JL, Lingwood CA (1995)Int J Biol Macromol 17: 199–205.
Grant CWM, Mehlhorn IE, Florio E, Barber KR (1987)Biochim Biophys Acta 902: 169–77.
Boggs J, Koshy K, Rangaraj G (1988)Biochim Biophys Acta 938: 373–85.
Boggs JM, Koshy KM (1994)Biochem Biophys Acta 1189: 233–41.
Morrow MR, Singh D, Lu D, Grant CWM (1993)Biophys J 64: 654–64.
Maggio B (1994)Prog Biophys Molec Biol 62: 55–117.
Singh D, Jarrell HC, Barber KR, Grant CWM (1992)Biochem 31: 3662–69.
Yang J, Tamm L, Tillack T, Shao Z (1993)J Mol Biol 229: 286–90.
Prasadarao NV, Wass CA, Hacker J, Jann K, Kim KS (1993)J Biol Chem 268: 10356–63.
Pancake SJ, Holt GD, Mellouk S, Hoffman SL (1992)J Cell Biol a117: 1351–57.
Krivan HC, Ginsburg V, Roberts DD (1988)Arch Biochem Biophys 260: 493–96.
Jimenez-Lucho V, Ginsburg V, Krivan H (1990)Infect Immun 58: 2085–90.
Kyogashima M, Ginsburg V, Krivan HC (1989)Arch Biochem Biophys 270: 391–97.
Karlsson K-A, Stromberg N (1987)Methods Enzymol 138: 220–32.
Jarrell HC, Jovall PA, Giziewicz JB, Turner LA, Smith CP (1987)Biochemistry 26: 1805.
Renou J, Giziewicz J, Smith I, Jarrell H (1989)Biochemistry 28: 1804–14.
Quill H, Carlson L, Fox B, Weistein J, Schwartz R (1987)J Imunol Meth 98: 29–41.
Watts T, Brian A, Kappler J, Marrack P, McConnell H (1984)Proc Natl Acad Sci USA 81: 7564–68.
McConnell H, Watts T, Weis R, Brian A (1985)Biochim Biophys Acta 864: 95–106.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Arab, S., Lingwood, C.A. Influence of phospholipid chain length on verotoxin/globotriaosyl ceramide binding in model membranes: comparison of a supported bilayer film and liposomes. Glycoconjugate J 13, 159–166 (1996). https://doi.org/10.1007/BF00731490
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00731490