Abstract
The Gag protein of Rous sarcoma virus (RSV) can direct particle assembly and budding at the plasma membrane independently of the other virus-encoded products. A previous deletion analysis has suggested that the first 86 amino acids of RSV Gag constitute a large membrane-binding domain that is absolutely required for these processes. To test this hypothesis, we inserted these residues in place of the N-terminal membrane-binding domain of the pp60v-src, a transforming protein whose biological activity requires plasma membrane localization. The ability of the Src chimera to induce cellular transformation suggests that the RSV sequence indeed contains an independent, functional domain.
Full Text
The Full Text of this article is available as a PDF (806.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bennett R. P., Nelle T. D., Wills J. W. Functional chimeras of the Rous sarcoma virus and human immunodeficiency virus gag proteins. J Virol. 1993 Nov;67(11):6487–6498. doi: 10.1128/jvi.67.11.6487-6498.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buser C. A., Sigal C. T., Resh M. D., McLaughlin S. Membrane binding of myristylated peptides corresponding to the NH2 terminus of Src. Biochemistry. 1994 Nov 8;33(44):13093–13101. doi: 10.1021/bi00248a019. [DOI] [PubMed] [Google Scholar]
- Buss J. E., Kamps M. P., Gould K., Sefton B. M. The absence of myristic acid decreases membrane binding of p60src but does not affect tyrosine protein kinase activity. J Virol. 1986 May;58(2):468–474. doi: 10.1128/jvi.58.2.468-474.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cross F. R., Garber E. A., Pellman D., Hanafusa H. A short sequence in the p60src N terminus is required for p60src myristylation and membrane association and for cell transformation. Mol Cell Biol. 1984 Sep;4(9):1834–1842. doi: 10.1128/mcb.4.9.1834. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Erdie C. R., Wills J. W. Myristylation of Rous sarcoma virus Gag protein does not prevent replication in avian cells. J Virol. 1990 Oct;64(10):5204–5208. doi: 10.1128/jvi.64.10.5204-5208.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fäcke M., Janetzko A., Shoeman R. L., Kräusslich H. G. A large deletion in the matrix domain of the human immunodeficiency virus gag gene redirects virus particle assembly from the plasma membrane to the endoplasmic reticulum. J Virol. 1993 Aug;67(8):4972–4980. doi: 10.1128/jvi.67.8.4972-4980.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gebhardt A., Bosch J. V., Ziemiecki A., Friis R. R. Rous sarcoma virus p19 and gp35 can be chemically crosslinked to high molecular weight complexes. An insight into virus assembly. J Mol Biol. 1984 Apr 5;174(2):297–317. doi: 10.1016/0022-2836(84)90340-1. [DOI] [PubMed] [Google Scholar]
- Jørgensen E. C., Pedersen F. S., Jørgensen P. Matrix protein of Akv murine leukemia virus: genetic mapping of regions essential for particle formation. J Virol. 1992 Jul;66(7):4479–4487. doi: 10.1128/jvi.66.7.4479-4487.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kamps M. P., Buss J. E., Sefton B. M. Mutation of NH2-terminal glycine of p60src prevents both myristoylation and morphological transformation. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4625–4628. doi: 10.1073/pnas.82.14.4625. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaplan J. M., Mardon G., Bishop J. M., Varmus H. E. The first seven amino acids encoded by the v-src oncogene act as a myristylation signal: lysine 7 is a critical determinant. Mol Cell Biol. 1988 Jun;8(6):2435–2441. doi: 10.1128/mcb.8.6.2435. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krueger J. G., Garber E. A., Goldberg A. R. Subcellular localization of pp60src in RSV-transformed cells. Curr Top Microbiol Immunol. 1983;107:51–124. [PubMed] [Google Scholar]
- Lipsich L. A., Lewis A. J., Brugge J. S. Isolation of monoclonal antibodies that recognize the transforming proteins of avian sarcoma viruses. J Virol. 1983 Nov;48(2):352–360. doi: 10.1128/jvi.48.2.352-360.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Massiah M. A., Starich M. R., Paschall C., Summers M. F., Christensen A. M., Sundquist W. I. Three-dimensional structure of the human immunodeficiency virus type 1 matrix protein. J Mol Biol. 1994 Nov 25;244(2):198–223. doi: 10.1006/jmbi.1994.1719. [DOI] [PubMed] [Google Scholar]
- Matthews S., Barlow P., Boyd J., Barton G., Russell R., Mills H., Cunningham M., Meyers N., Burns N., Clark N. Structural similarity between the p17 matrix protein of HIV-1 and interferon-gamma. Nature. 1994 Aug 25;370(6491):666–668. doi: 10.1038/370666a0. [DOI] [PubMed] [Google Scholar]
- McLaughlin S., Aderem A. The myristoyl-electrostatic switch: a modulator of reversible protein-membrane interactions. Trends Biochem Sci. 1995 Jul;20(7):272–276. doi: 10.1016/s0968-0004(00)89042-8. [DOI] [PubMed] [Google Scholar]
- Nelle T. D., Wills J. W. A large region within the Rous sarcoma virus matrix protein is dispensable for budding and infectivity. J Virol. 1996 Apr;70(4):2269–2276. doi: 10.1128/jvi.70.4.2269-2276.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parent L. J., Bennett R. P., Craven R. C., Nelle T. D., Krishna N. K., Bowzard J. B., Wilson C. B., Puffer B. A., Montelaro R. C., Wills J. W. Positionally independent and exchangeable late budding functions of the Rous sarcoma virus and human immunodeficiency virus Gag proteins. J Virol. 1995 Sep;69(9):5455–5460. doi: 10.1128/jvi.69.9.5455-5460.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Peitzsch R. M., McLaughlin S. Binding of acylated peptides and fatty acids to phospholipid vesicles: pertinence to myristoylated proteins. Biochemistry. 1993 Oct 5;32(39):10436–10443. doi: 10.1021/bi00090a020. [DOI] [PubMed] [Google Scholar]
- Pepinsky R. B., Cappiello D., Wilkowski C., Vogt V. M. Chemical crosslinking of proteins in avian sarcoma and leukemia viruses. Virology. 1980 Apr 15;102(1):205–210. doi: 10.1016/0042-6822(80)90081-1. [DOI] [PubMed] [Google Scholar]
- Pepinsky R. B. Localization of lipid-protein and protein-protein interactions within the murine retrovirus gag precursor by a novel peptide-mapping technique. J Biol Chem. 1983 Sep 25;258(18):11229–11235. [PubMed] [Google Scholar]
- Pepinsky R. B., Vogt V. M. Fine-structure analyses of lipid-protein and protein-protein interactions of gag protein p19 of the avian sarcoma and leukemia viruses by cyanogen bromide mapping. J Virol. 1984 Oct;52(1):145–153. doi: 10.1128/jvi.52.1.145-153.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pepinsky R. B., Vogt V. M. Identification of retrovirus matrix proteins by lipid-protein cross-linking. J Mol Biol. 1979 Jul 15;131(4):819–837. doi: 10.1016/0022-2836(79)90203-1. [DOI] [PubMed] [Google Scholar]
- Rhee S. S., Hunter E. Structural role of the matrix protein of type D retroviruses in gag polyprotein stability and capsid assembly. J Virol. 1990 Sep;64(9):4383–4389. doi: 10.1128/jvi.64.9.4383-4389.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rohrschneider L. R. Adhesion plaques of Rous sarcoma virus-transformed cells contain the src gene product. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3514–3518. doi: 10.1073/pnas.77.6.3514. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rohrschneider L., Reynolds S. Regulation of cellular morphology by the Rous sarcoma virus src gene: analysis of fusiform mutants. Mol Cell Biol. 1985 Nov;5(11):3097–3107. doi: 10.1128/mcb.5.11.3097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schultz A. M., Henderson L. E., Oroszlan S. Fatty acylation of proteins. Annu Rev Cell Biol. 1988;4:611–647. doi: 10.1146/annurev.cb.04.110188.003143. [DOI] [PubMed] [Google Scholar]
- Shin S. I., Freedman V. H., Risser R., Pollack R. Tumorigenicity of virus-transformed cells in nude mice is correlated specifically with anchorage independent growth in vitro. Proc Natl Acad Sci U S A. 1975 Nov;72(11):4435–4439. doi: 10.1073/pnas.72.11.4435. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sigal C. T., Zhou W., Buser C. A., McLaughlin S., Resh M. D. Amino-terminal basic residues of Src mediate membrane binding through electrostatic interaction with acidic phospholipids. Proc Natl Acad Sci U S A. 1994 Dec 6;91(25):12253–12257. doi: 10.1073/pnas.91.25.12253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Verderame M. F., Kaplan J. M., Varmus H. E. A mutation in v-src that removes a single conserved residue in the SH-2 domain of pp60v-src restricts transformation in a host-dependent manner. J Virol. 1989 Jan;63(1):338–348. doi: 10.1128/jvi.63.1.338-348.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vogt V. M., Eisenman R., Diggelmann H. Generation of avian myeloblastosis virus structural proteins by proteolytic cleavage of a precursor polypeptide. J Mol Biol. 1975 Aug 15;96(3):471–493. doi: 10.1016/0022-2836(75)90174-6. [DOI] [PubMed] [Google Scholar]
- Vogt V. M., Pepinsky R. B., Southard L. E. Primary structure of p19 species of avian sarcoma and leukemia viruses. J Virol. 1985 Oct;56(1):31–39. doi: 10.1128/jvi.56.1.31-39.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weintraub H., Tapscott S. J., Davis R. L., Thayer M. J., Adam M. A., Lassar A. B., Miller A. D. Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5434–5438. doi: 10.1073/pnas.86.14.5434. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wills J. W., Craven R. C., Achacoso J. A. Creation and expression of myristylated forms of Rous sarcoma virus gag protein in mammalian cells. J Virol. 1989 Oct;63(10):4331–4343. doi: 10.1128/jvi.63.10.4331-4343.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wills J. W., Craven R. C. Form, function, and use of retroviral gag proteins. AIDS. 1991 Jun;5(6):639–654. doi: 10.1097/00002030-199106000-00002. [DOI] [PubMed] [Google Scholar]
- Wills J. W., Craven R. C., Weldon R. A., Jr, Nelle T. D., Erdie C. R. Suppression of retroviral MA deletions by the amino-terminal membrane-binding domain of p60src. J Virol. 1991 Jul;65(7):3804–3812. doi: 10.1128/jvi.65.7.3804-3812.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Woods K. M., Verderame M. F. Autophosphorylation is required for high kinase activity and efficient transformation ability of proteins encoded by host range alleles of v-src. J Virol. 1994 Nov;68(11):7267–7274. doi: 10.1128/jvi.68.11.7267-7274.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yu X., Yuan X., Matsuda Z., Lee T. H., Essex M. The matrix protein of human immunodeficiency virus type 1 is required for incorporation of viral envelope protein into mature virions. J Virol. 1992 Aug;66(8):4966–4971. doi: 10.1128/jvi.66.8.4966-4971.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yuan X., Yu X., Lee T. H., Essex M. Mutations in the N-terminal region of human immunodeficiency virus type 1 matrix protein block intracellular transport of the Gag precursor. J Virol. 1993 Nov;67(11):6387–6394. doi: 10.1128/jvi.67.11.6387-6394.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zhou W., Parent L. J., Wills J. W., Resh M. D. Identification of a membrane-binding domain within the amino-terminal region of human immunodeficiency virus type 1 Gag protein which interacts with acidic phospholipids. J Virol. 1994 Apr;68(4):2556–2569. doi: 10.1128/jvi.68.4.2556-2569.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]