1. Structural Biology and Molecular Biophysics
Download icon

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
  • Cited 0
  • Views 830
  • Annotations
Cite this article as: eLife 2020;9:e58621 doi: 10.7554/eLife.58621


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
    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


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)


© 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.


  • 830
    Page views
  • 155
  • 0

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Structural Biology and Molecular Biophysics
    Daniel K Weber et al.
    Research Article

    Phospholamban (PLN) is a mini-membrane protein that directly controls the cardiac Ca2+-transport response to b-adrenergic stimulation, thus modulating cardiac output during the fight-or-flight response. In the sarcoplasmic reticulum membrane, PLN binds to the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA), keeping this enzyme's function within a narrow physiological window. PLN phosphorylation by cAMP-dependent protein kinase A or increase in Ca2+ concentration reverses the inhibitory effects through an unknown mechanism. Using oriented-sample solid-state NMR spectroscopy and replica-averaged NMR-restrained structural refinement, we reveal that phosphorylation of PLN;s cytoplasmic regulatory domain signals the disruption of several inhibitory contacts at the transmembrane binding interface of the SERCA-PLN complex that are propagated to the enzyme;s active site, augmenting Ca2+ transport. Our findings address long-standing questions about SERCA regulation, epitomizing a signal transduction mechanism operated by posttranslationally modified bitopic membrane proteins.

    1. Chromosomes and Gene Expression
    2. Structural Biology and Molecular Biophysics
    Laura Plassart et al.
    Research Article Updated

    Preventing premature interaction of pre-ribosomes with the translation apparatus is essential for translational accuracy. Hence, the final maturation step releasing functional 40S ribosomal subunits, namely processing of the 18S ribosomal RNA 3′ end, is safeguarded by the protein DIM2, which both interacts with the endoribonuclease NOB1 and masks the rRNA cleavage site. To elucidate the control mechanism that unlocks NOB1 activity, we performed cryo-electron microscopy analysis of late human pre-40S particles purified using a catalytically inactive form of the ATPase RIO1. These structures, together with in vivo and in vitro functional analyses, support a model in which ATP-loaded RIO1 cooperates with ribosomal protein RPS26/eS26 to displace DIM2 from the 18S rRNA 3′ end, thereby triggering final cleavage by NOB1; release of ADP then leads to RIO1 dissociation from the 40S subunit. This dual key lock mechanism requiring RIO1 and RPS26 guarantees the precise timing of pre-40S particle conversion into translation-competent ribosomal subunits.