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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.
J Biol Chem. 2018 12 07; 293(49):18841-18853.JB

Abstract

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.

Authors+Show Affiliations

From the Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11794 and.From the Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11794 and.the Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294.the Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294.the Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294.the Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294.From the Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11794 and carol.carter@stonybrook.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

30309982

Citation

Watanabe, Susan M., et al. "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." The Journal of Biological Chemistry, vol. 293, no. 49, 2018, pp. 18841-18853.
Watanabe SM, Medina GN, Eastep GN, et al. 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. J Biol Chem. 2018;293(49):18841-18853.
Watanabe, S. M., Medina, G. N., Eastep, G. N., Ghanam, R. H., Vlach, J., Saad, J. S., & Carter, C. A. (2018). 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. The Journal of Biological Chemistry, 293(49), 18841-18853. https://doi.org/10.1074/jbc.RA118.003947
Watanabe SM, et al. 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. J Biol Chem. 2018 12 7;293(49):18841-18853. PubMed PMID: 30309982.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Watanabe,Susan M, AU - Medina,Gisselle N, AU - Eastep,Gunnar N, AU - Ghanam,Ruba H, AU - Vlach,Jiri, AU - Saad,Jamil S, AU - Carter,Carol A, Y1 - 2018/10/11/ PY - 2018/05/13/received PY - 2018/09/28/revised PY - 2018/10/13/pubmed PY - 2019/4/18/medline PY - 2018/10/13/entrez KW - ASV KW - Gag protein KW - avian sarcoma virus KW - human immunodeficiency virus (HIV) KW - myristoylated matrix KW - phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) KW - plasma membrane KW - protein myristoylation KW - protein structure KW - viral budding KW - virus assembly SP - 18841 EP - 18853 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 293 IS - 49 N2 - 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. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/30309982/The_matrix_domain_of_the_Gag_protein_from_avian_sarcoma_virus_contains_a_PI_45_P2_binding_site_that_targets_Gag_to_the_cell_periphery_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=30309982 DB - PRIME DP - Unbound Medicine ER -