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. 1995 Oct 10;92(21):9871–9875. doi: 10.1073/pnas.92.21.9871

The human and simian immunodeficiency virus envelope glycoprotein transmembrane subunits are palmitoylated.

C Yang 1, C P Spies 1, R W Compans 1
PMCID: PMC40904  PMID: 7568235

Abstract

The envelope proteins of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) were found to be modified by fatty acylation of the transmembrane protein subunit gp41. The precursor gp160 was also palmitoylated prior to its cleavage into the gp120 and gp41 subunits. The palmitic acid label was sensitive to treatment with hydroxylamine or 2-mercaptoethanol, indicating that the linkage is through a thioester bond. Treatment with cycloheximide did not prevent the incorporation of [3H]palmitic acid into the HIV envelope protein, indicating that palmitoylation is a posttranslation modification. In contrast to other glycoproteins, which are palmitoylated at cysteine residues within or close to the membrane-spanning hydrophobic domain, the palmitoylation of the HIV-1 envelope proteins occurs on two cysteine residues, Cys-764 and Cys-837, which are 59 and 132 amino acids, respectively, from the proposed membrane-spanning domain of gp41. Sequence comparison revealed that one of these residues (Cys-764) is conserved in the cytoplasmic domains of almost all HIV-1 isolates and is located very close to an amphipathic region which has been postulated to bind to the plasma membrane.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allan J. S., Coligan J. E., Barin F., McLane M. F., Sodroski J. G., Rosen C. A., Haseltine W. A., Lee T. H., Essex M. Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III. Science. 1985 May 31;228(4703):1091–1094. doi: 10.1126/science.2986290. [DOI] [PubMed] [Google Scholar]
  2. Alvarez E., Gironès N., Davis R. J. Inhibition of the receptor-mediated endocytosis of diferric transferrin is associated with the covalent modification of the transferrin receptor with palmitic acid. J Biol Chem. 1990 Sep 25;265(27):16644–16655. [PubMed] [Google Scholar]
  3. Anand R., Thayer R., Srinivasan A., Nayyar S., Gardner M., Luciw P., Dandekar S. Biological and molecular characterization of human immunodeficiency virus (HIV-1BR) from the brain of a patient with progressive dementia. Virology. 1989 Jan;168(1):79–89. doi: 10.1016/0042-6822(89)90406-6. [DOI] [PubMed] [Google Scholar]
  4. Bernstein H. B., Compans R. W. Sulfation of the human immunodeficiency virus envelope glycoprotein. J Virol. 1992 Dec;66(12):6953–6959. doi: 10.1128/jvi.66.12.6953-6959.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bernstein H. B., Tucker S. P., Hunter E., Schutzbach J. S., Compans R. W. Human immunodeficiency virus type 1 envelope glycoprotein is modified by O-linked oligosaccharides. J Virol. 1994 Jan;68(1):463–468. doi: 10.1128/jvi.68.1.463-468.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cadwallader K. A., Paterson H., Macdonald S. G., Hancock J. F. N-terminally myristoylated Ras proteins require palmitoylation or a polybasic domain for plasma membrane localization. Mol Cell Biol. 1994 Jul;14(7):4722–4730. doi: 10.1128/mcb.14.7.4722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Camp L. A., Hofmann S. L. Purification and properties of a palmitoyl-protein thioesterase that cleaves palmitate from H-Ras. J Biol Chem. 1993 Oct 25;268(30):22566–22574. [PubMed] [Google Scholar]
  8. Charneau P., Borman A. M., Quillent C., Guétard D., Chamaret S., Cohen J., Rémy G., Montagnier L., Clavel F. Isolation and envelope sequence of a highly divergent HIV-1 isolate: definition of a new HIV-1 group. Virology. 1994 Nov 15;205(1):247–253. doi: 10.1006/viro.1994.1640. [DOI] [PubMed] [Google Scholar]
  9. Crise B., Rose J. K. Identification of palmitoylation sites on CD4, the human immunodeficiency virus receptor. J Biol Chem. 1992 Jul 5;267(19):13593–13597. [PubMed] [Google Scholar]
  10. Dubay J. W., Roberts S. J., Hahn B. H., Hunter E. Truncation of the human immunodeficiency virus type 1 transmembrane glycoprotein cytoplasmic domain blocks virus infectivity. J Virol. 1992 Nov;66(11):6616–6625. doi: 10.1128/jvi.66.11.6616-6625.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eason M. G., Jacinto M. T., Theiss C. T., Liggett S. B. The palmitoylated cysteine of the cytoplasmic tail of alpha 2A-adrenergic receptors confers subtype-specific agonist-promoted downregulation. Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):11178–11182. doi: 10.1073/pnas.91.23.11178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fuerst T. R., Niles E. G., Studier F. W., Moss B. Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8122–8126. doi: 10.1073/pnas.83.21.8122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gabuzda D. H., Lever A., Terwilliger E., Sodroski J. Effects of deletions in the cytoplasmic domain on biological functions of human immunodeficiency virus type 1 envelope glycoproteins. J Virol. 1992 Jun;66(6):3306–3315. doi: 10.1128/jvi.66.6.3306-3315.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gallaher W. R., Ball J. M., Garry R. F., Griffin M. C., Montelaro R. C. A general model for the transmembrane proteins of HIV and other retroviruses. AIDS Res Hum Retroviruses. 1989 Aug;5(4):431–440. doi: 10.1089/aid.1989.5.431. [DOI] [PubMed] [Google Scholar]
  15. Gallaher W. R. Detection of a fusion peptide sequence in the transmembrane protein of human immunodeficiency virus. Cell. 1987 Jul 31;50(3):327–328. doi: 10.1016/0092-8674(87)90485-5. [DOI] [PubMed] [Google Scholar]
  16. Geyer H., Holschbach C., Hunsmann G., Schneider J. Carbohydrates of human immunodeficiency virus. Structures of oligosaccharides linked to the envelope glycoprotein 120. J Biol Chem. 1988 Aug 25;263(24):11760–11767. [PubMed] [Google Scholar]
  17. Gurgo C., Guo H. G., Franchini G., Aldovini A., Collalti E., Farrell K., Wong-Staal F., Gallo R. C., Reitz M. S., Jr Envelope sequences of two new United States HIV-1 isolates. Virology. 1988 Jun;164(2):531–536. doi: 10.1016/0042-6822(88)90568-5. [DOI] [PubMed] [Google Scholar]
  18. Hallenberger S., Bosch V., Angliker H., Shaw E., Klenk H. D., Garten W. Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160. Nature. 1992 Nov 26;360(6402):358–361. doi: 10.1038/360358a0. [DOI] [PubMed] [Google Scholar]
  19. Kaufman J. F., Krangel M. S., Strominger J. L. Cysteines in the transmembrane region of major histocompatibility complex antigens are fatty acylated via thioester bonds. J Biol Chem. 1984 Jun 10;259(11):7230–7238. [PubMed] [Google Scholar]
  20. Kestler H., Kodama T., Ringler D., Marthas M., Pedersen N., Lackner A., Regier D., Sehgal P., Daniel M., King N. Induction of AIDS in rhesus monkeys by molecularly cloned simian immunodeficiency virus. Science. 1990 Jun 1;248(4959):1109–1112. doi: 10.1126/science.2160735. [DOI] [PubMed] [Google Scholar]
  21. Kong L. I., Lee S. W., Kappes J. C., Parkin J. S., Decker D., Hoxie J. A., Hahn B. H., Shaw G. M. West African HIV-2-related human retrovirus with attenuated cytopathicity. Science. 1988 Jun 10;240(4858):1525–1529. doi: 10.1126/science.3375832. [DOI] [PubMed] [Google Scholar]
  22. Kowalski M., Potz J., Basiripour L., Dorfman T., Goh W. C., Terwilliger E., Dayton A., Rosen C., Haseltine W., Sodroski J. Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1. Science. 1987 Sep 11;237(4820):1351–1355. doi: 10.1126/science.3629244. [DOI] [PubMed] [Google Scholar]
  23. Koyanagi Y., Miles S., Mitsuyasu R. T., Merrill J. E., Vinters H. V., Chen I. S. Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science. 1987 May 15;236(4803):819–822. doi: 10.1126/science.3646751. [DOI] [PubMed] [Google Scholar]
  24. Kozarsky K., Penman M., Basiripour L., Haseltine W., Sodroski J., Krieger M. Glycosylation and processing of the human immunodeficiency virus type 1 envelope protein. J Acquir Immune Defic Syndr. 1989;2(2):163–169. [PubMed] [Google Scholar]
  25. Kunkel T. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985 Jan;82(2):488–492. doi: 10.1073/pnas.82.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  27. Lee S. J., Hu W., Fisher A. G., Looney D. J., Kao V. F., Mitsuya H., Ratner L., Wong-Staal F. Role of the carboxy-terminal portion of the HIV-1 transmembrane protein in viral transmission and cytopathogenicity. AIDS Res Hum Retroviruses. 1989 Aug;5(4):441–449. doi: 10.1089/aid.1989.5.441. [DOI] [PubMed] [Google Scholar]
  28. Levy J. A. Pathogenesis of human immunodeficiency virus infection. Microbiol Rev. 1993 Mar;57(1):183–289. doi: 10.1128/mr.57.1.183-289.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Li Y., Luo L., Rasool N., Kang C. Y. Glycosylation is necessary for the correct folding of human immunodeficiency virus gp120 in CD4 binding. J Virol. 1993 Jan;67(1):584–588. doi: 10.1128/jvi.67.1.584-588.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Louwagie J., Janssens W., Mascola J., Heyndrickx L., Hegerich P., van der Groen G., McCutchan F. E., Burke D. S. Genetic diversity of the envelope glycoprotein from human immunodeficiency virus type 1 isolates of African origin. J Virol. 1995 Jan;69(1):263–271. doi: 10.1128/jvi.69.1.263-271.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Matthews T. J., Weinhold K. J., Lyerly H. K., Langlois A. J., Wigzell H., Bolognesi D. P. Interaction between the human T-cell lymphotropic virus type IIIB envelope glycoprotein gp120 and the surface antigen CD4: role of carbohydrate in binding and cell fusion. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5424–5428. doi: 10.1073/pnas.84.15.5424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mumby S. M., Kleuss C., Gilman A. G. Receptor regulation of G-protein palmitoylation. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2800–2804. doi: 10.1073/pnas.91.7.2800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Naim H. Y., Amarneh B., Ktistakis N. T., Roth M. G. Effects of altering palmitylation sites on biosynthesis and function of the influenza virus hemagglutinin. J Virol. 1992 Dec;66(12):7585–7588. doi: 10.1128/jvi.66.12.7585-7588.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Nussbaum O., Broder C. C., Berger E. A. Fusogenic mechanisms of enveloped-virus glycoproteins analyzed by a novel recombinant vaccinia virus-based assay quantitating cell fusion-dependent reporter gene activation. J Virol. 1994 Sep;68(9):5411–5422. doi: 10.1128/jvi.68.9.5411-5422.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. O'Dowd B. F., Hnatowich M., Caron M. G., Lefkowitz R. J., Bouvier M. Palmitoylation of the human beta 2-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor. J Biol Chem. 1989 May 5;264(13):7564–7569. [PubMed] [Google Scholar]
  36. Owens R. J., Dubay J. W., Hunter E., Compans R. W. Human immunodeficiency virus envelope protein determines the site of virus release in polarized epithelial cells. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3987–3991. doi: 10.1073/pnas.88.9.3987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Resh M. D. Myristylation and palmitylation of Src family members: the fats of the matter. Cell. 1994 Feb 11;76(3):411–413. doi: 10.1016/0092-8674(94)90104-x. [DOI] [PubMed] [Google Scholar]
  38. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Schmidt M. F., Bracha M., Schlesinger M. J. Evidence for covalent attachment of fatty acids to Sindbis virus glycoproteins. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1687–1691. doi: 10.1073/pnas.76.4.1687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Schmidt M. F. Fatty acylation of proteins. Biochim Biophys Acta. 1989 Dec 6;988(3):411–426. doi: 10.1016/0304-4157(89)90013-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Schmidt M. F., Schlesinger M. J. Fatty acid binding to vesicular stomatitis virus glycoprotein: a new type of post-translational modification of the viral glycoprotein. Cell. 1979 Aug;17(4):813–819. doi: 10.1016/0092-8674(79)90321-0. [DOI] [PubMed] [Google Scholar]
  42. Spies C. P., Compans R. W. Effects of cytoplasmic domain length on cell surface expression and syncytium-forming capacity of the simian immunodeficiency virus envelope glycoprotein. Virology. 1994 Aug 15;203(1):8–19. doi: 10.1006/viro.1994.1449. [DOI] [PubMed] [Google Scholar]
  43. Srinivas S. K., Srinivas R. V., Anantharamaiah G. M., Segrest J. P., Compans R. W. Membrane interactions of synthetic peptides corresponding to amphipathic helical segments of the human immunodeficiency virus type-1 envelope glycoprotein. J Biol Chem. 1992 Apr 5;267(10):7121–7127. [PubMed] [Google Scholar]
  44. Takeuchi Y., Akutsu M., Murayama K., Shimizu N., Hoshino H. Host range mutant of human immunodeficiency virus type 1: modification of cell tropism by a single point mutation at the neutralization epitope in the env gene. J Virol. 1991 Apr;65(4):1710–1718. doi: 10.1128/jvi.65.4.1710-1718.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Venable R. M., Pastor R. W., Brooks B. R., Carson F. W. Theoretically determined three-dimensional structures for amphipathic segments of the HIV-1 gp41 envelope protein. AIDS Res Hum Retroviruses. 1989 Feb;5(1):7–22. doi: 10.1089/aid.1989.5.7. [DOI] [PubMed] [Google Scholar]
  46. Wedegaertner P. B., Chu D. H., Wilson P. T., Levis M. J., Bourne H. R. Palmitoylation is required for signaling functions and membrane attachment of Gq alpha and Gs alpha. J Biol Chem. 1993 Nov 25;268(33):25001–25008. [PubMed] [Google Scholar]
  47. Willey R. L., Bonifacino J. S., Potts B. J., Martin M. A., Klausner R. D. Biosynthesis, cleavage, and degradation of the human immunodeficiency virus 1 envelope glycoprotein gp160. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580–9584. doi: 10.1073/pnas.85.24.9580. [DOI] [PMC free article] [PubMed] [Google Scholar]

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