ArticleProceedings of the National Academy of Sciences of the United States of America2010
Opposing mechanisms involving RNA and lipids regulate HIV-1 Gag membrane binding through the highly basic region of the matrix domain.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers, 1 of them a synthesis that pooled it.
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Who cites it
168 citing papers in PubMed, 1 synthesis or guideline pooled it, 218 citations in OpenAlex.
- HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016Pooled it
- Mechanisms of HIV-1 assembly, release and maturation.Nature reviews. Microbiology · 2026Review
- Identification of Non-basic Matrix Domain Residues That Impact HTLV-1 Gag Membrane Targeting and Particle Release.Journal of molecular biology · 2026Article
- Cryo-ET reveals distinct Gag lattice architectures in virus-like particles and immature HIV-1.Structure (London, England : 1993) · 2026Article
- M-Sec promotes the production of infectious HIV-1 virus through the exocyst complex in macrophages.PLoS pathogens · 2026Article
- Beyond reverse transcription: molecular mechanisms and emerging paradigms in retroviral replication.FEMS microbiology reviews · 2026Review
- Evasion of CARD8 activation during HIV-1 assembly.Science advances · 2025Article
- Positive correlation between structural disorder of the HIV-1 Gag N-terminal segment and progeny virus particle formation.Journal of virology · 2025Article
- The role of HIV-1 Gag and genomic RNA interactions in virion assembly.Frontiers in microbiology · 2025Article
- Review
- The Assembly of HTLV-1-How Does It Differ from HIV-1?Viruses · 2024Review
- HIV-1 Gag Polyprotein Affinity to the Lipid Membrane Is Independent of Its Surface Charge.Biomolecules · 2024Article
- HIV-1 RNA genome packaging: it's G-rated.mBio · 2024Review
- The "basics" of HIV-1 assembly.PLoS pathogens · 2024Article
- Dissecting membrane interfacial cellular processes: an in vitro reconstitution approach.The European physical journal. Special topics · 2024Review
- Influence of HIV-1 Genomic RNA on the Formation of Gag Biomolecular Condensates.Journal of molecular biology · 2023Article
- Quantifying membrane binding and diffusion with fluorescence correlation spectroscopy diffusion laws.Biophysical journal · 2023Article
- Article
- Partitioning of ribonucleoprotein complexes from the cellular actin cortex.Science advances · 2022Article
- HIV-1 mutants expressing B cell clonogenic matrix protein p17 variants are increasing their prevalence worldwide.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
108 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Membrane binding of Gag, a crucial step in HIV-1 assembly, is facilitated by bipartite signals within the matrix (MA) domain: N-terminal myristoyl moiety and the highly basic region (HBR). We and others have shown that Gag interacts with a plasma-membrane-specific acidic phospholipid, phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P(2)], via the HBR, and that this interaction is important for efficient membrane binding and plasma membrane targeting of Gag. Generally, in protein-PI(4,5)P(2) interactions, basic residues promote the interaction as docking sites for the acidic headgroup of the lipid. In this study, toward better understanding of the Gag-PI(4,5)P(2) interaction, we sought to determine the roles played by all of the basic residues in the HBR. We identified three basic residues promoting PI(4,5)P(2)-dependent Gag-membrane binding. Unexpectedly, two other HBR residues, Lys25 and Lys26, suppress membrane binding in the absence of PI(4,5)P(2) and prevent promiscuous intracellular localization of Gag. This inhibition of nonspecific membrane binding is likely through suppression of myristate-dependent hydrophobic interaction because mutating Lys25 and Lys26 enhances binding of Gag with neutral-charged liposomes. These residues were reported to bind RNA. Importantly, we found that RNA also negatively regulates Gag membrane binding. In the absence but not presence of PI(4,5)P(2), RNA bound to MA HBR abolishes Gag-liposome binding. Altogether, these data indicate that the HBR is unique among basic phosphoinositide-binding domains, because it integrates three regulatory components, PI(4,5)P(2), myristate, and RNA, to ensure plasma membrane specificity for particle assembly.
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