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Membrane Binding of HIV-1 Matrix Protein: Dependence on Bilayer Composition and Protein Lipidation

Published

Author(s)

Marilia Barros, Frank Heinrich, Siddhartha A. K. Datta, Alan Rein, Ioannis Karageorgos, Hirsh Nanda, Mathias Loesche

Abstract

Retroviral Gag polyprotein is the structural determinant that assembles in a protein lattice on the host's plasma membrane to trigger formation of the viral protein/membrane shell. In this process, it employs multiple signals - electrostatic, hydrophobic and lipid-specific interactions conferred by the matrix domain - to recruit the protein to the proper cellular location and assist protein-protein interactions located on full-length Gag in lattice formation. We report the interaction of non-lipidated and myristoylated HIV-1 Gag matrix domains with bilayers composed of purified lipid components to dissect these complex membrane signals and quantify their contributions to the overall interaction. SPR on well-defined membrane models is used to quantify binding affinities and amounts of protein and yields free binding energy contributions, Δ}G, of the various signals. Charge-charge interactions in the absence of the phosphatidylinositide PI(4,5)P2 attract the protein to acidic membrane surfaces, and myristoylation increases the affinity by a factor of 10, arguing against a PI(4,5)P2-trigger of myristate exposure. Lipid-specific interactions wit the PI(4,5)P2, the major signal lipid in the inner plasma membrane, increase membrane attraction at a similar level as the protein lipidation. While cholesterol does not directly engage in interactions, it augments protein affinity strongly, apparently by unlocking steric obstacles to efficient myristate insertion and PI(4,5)P2 binding. We thus observe that the isolated matrix protein, in the absence of protein-protein interaction conferred by the full-length Gag, binds the membrane with sub-micromolar affinities.
Citation
Journal of Virology
Volume
90
Issue
9

Keywords

surface plasmon resonance, HIV Gag matrix, membrane binding

Citation

Barros, M. , Heinrich, F. , Datta, S. , Rein, A. , Karageorgos, I. , Nanda, H. and Loesche, M. (2016), Membrane Binding of HIV-1 Matrix Protein: Dependence on Bilayer Composition and Protein Lipidation, Journal of Virology, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=919846 (Accessed May 29, 2023)
Created April 30, 2016, Updated October 12, 2021