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The matrix domain of the Gag protein from avian sarcoma virus contains a PI(4,5)P2-binding site that targets Gag to the cell periphery.
- Source :
-
Journal of Biological Chemistry . 12/7/2018, Vol. 293 Issue 49, p18841-18853. 13p. - Publication Year :
- 2018
-
Abstract
- The Gag protein of avian sarcoma virus (ASV) lacks anN-myristoyl (myr) group, but contains structural domains similar to those of HIV-1 Gag. Similarly to HIV-1, ASV Gag accumulates on the plasma membrane (PM) before egress; however, it is unclear whether the phospholipid PI(4,5)P2 binds directly to the matrix (MA) domain of ASV Gag, as is the case for HIV-1 Gag. Moreover, the role of PI(4,5)P2 in ASV Gag localization and budding has been controversial. Here, we report that substitution of residues that define the PI(4,5)P2-binding site in the ASV MAdomain (reported in an accompanying paper) interfere with Gag localization to the cell periphery and inhibit the production of virus-like particles (VLPs). We show that co-expression of Sprouty2 (Spry2) or the pleckstrin homology domain of phospholipaseC (PH-PLC), two proteins that bind PI(4,5)P2, affects ASV Gag trafficking to thePMand budding. Replacement of the N-terminal 32 residues of HIV-1 MA, which encode its N-terminal myr signal and its PI(4,5)P2-binding site, with the structurally equivalent N-terminal 24 residues of ASV MA created a chimera that localized at the PM and produced VLPs. In contrast, the homologous PI(4,5)P2-binding signal in ASV MA could target HIV-1 Gag to thePMwhen substituted, but did not support budding. Collectively, these findings reveal a basic patch in both ASV and HIV-1 Gag capable of mediating PM binding and budding for ASV but not for HIV-1 Gag. We conclude that PI(4,5)P2 is a strong determinant of ASV Gag targeting to the PM and budding. [ABSTRACT FROM AUTHOR]
- Subjects :
- *AVIAN sarcoma-leukosis virus
*GAG proteins
*PHOSPHOLIPASE C
*HIV
*PHOSPHOLIPIDS
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 293
- Issue :
- 49
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 133475461
- Full Text :
- https://doi.org/10.1074/jbc.RA118.003947