1. Structural Biology and Molecular Biophysics
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Binding mechanism of the matrix domain of HIV-1 Gag to lipid membranes

  1. Viviana Monje-Galvan
  2. Gregory A Voth  Is a corresponding author
  1. The University of Chicago, United States
Research Article
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Cite this article as: eLife 2020;9:e58621 doi: 10.7554/eLife.58621

Abstract

Specific protein-lipid interactions are critical for viral assembly. We present a molecular dynamics simulation study on the binding mechanism of the membrane targeting domain of HIV-1 Gag protein. The matrix (MA) domain drives Gag onto the plasma membrane through electrostatic interactions at its highly-basic-region (HBR), located near the myristoylated (Myr) N-terminus of the protein. Our study suggests Myr insertion is involved in the sorting of membrane lipids around the protein binding site to prepare it for viral assembly. Our realistic membrane models confirm interactions with PIP2 and PS lipids are highly favored around the HBR, and are strong enough to keep the protein bound even without Myr insertion. We characterized Myr insertion events from microsecond trajectories, and examined the membrane response upon initial membrane targeting by MA. Insertion events only occur with one of the membrane models, showing a combination of surface charge and internal membrane structure modulate this process.

Data availability

The simulation trajectories used for the analysis presented in this work are available at the Pittsburgh Supercomputing Center (PSC) Database for simulations run on the Anton2 Machine (http://psc.edu/anton-project-summaries?id=3071&pid=34).

The following data sets were generated

Article and author information

Author details

  1. Viviana Monje-Galvan

    Department of Chemistry, The University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Gregory A Voth

    Department of Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago, Chicago, United States
    For correspondence
    gavoth@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3267-6748

Funding

National Institute of General Medical Sciences (R01GM063796)

  • Viviana Monje-Galvan
  • Gregory A Voth

National Institutes of Health (R01GM116961)

  • Gregory A Voth

National Science Foundation (ACI-1548562)

  • Gregory A Voth

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. José D Faraldo-Gómez, National Heart, Lung and Blood Institute, National Institutes of Health, United States

Publication history

  1. Received: May 6, 2020
  2. Accepted: August 14, 2020
  3. Accepted Manuscript published: August 18, 2020 (version 1)
  4. Version of Record published: September 7, 2020 (version 2)

Copyright

© 2020, Monje-Galvan & Voth

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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