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
| Autor: | Jiri Vlach, Carol A. Carter, Gunnar N. Eastep, Jamil S. Saad, Ruba H. Ghanam, Gisselle N. Medina, Susan M. Watanabe |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
animal structures Chemistry viruses Viral budding myr Cell Biology Group-specific antigen Biochemistry Avian sarcoma virus Cell biology Pleckstrin homology domain 03 medical and health sciences 030104 developmental biology Protein structure embryonic structures Protein myristoylation Binding site Molecular Biology |
| Zdroj: | Journal of Biological Chemistry. 293:18841-18853 |
| ISSN: | 0021-9258 |
| Popis: | The Gag protein of avian sarcoma virus (ASV) lacks an N-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 MA domain (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 phospholipase Cδ (PH-PLC), two proteins that bind PI(4,5)P2, affects ASV Gag trafficking to the PM and 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 the PM when 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. |
| Databáze: | OpenAIRE |
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