ArticleProceedings of the National Academy of Sciences of the United States of America2016
Transient HIV-1 Gag-protease interactions revealed by paramagnetic NMR suggest origins of compensatory drug resistance mutations.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Inhibitors of HIV-1 maturation modulate conformational dynamics and heterogeneity of the immature Gag lattice.bioRxiv : the preprint server for biology · 2026Article
- Direct disassembly of α-syn preformed fibrils into α-syn monomers by an all-D-peptide.NPJ Parkinson's disease · 2025Article
- Subtype-Specific HIV-1 Protease and the Role of Hinge and Flap Dynamics in Drug Resistance: A Subtype C Narrative.Viruses · 2025Review
- Integrative Computational Approaches for Understanding Drug Resistance in HIV-1 Protease Subtype C.Viruses · 2025Review
- Probing Biomolecular Interactions with Paramagnetic Nuclear Magnetic Resonance Spectroscopy.Chembiochem : a European journal of chemical biology · 2025Review
- Article
- ALS Variants of Annexin A11's Proline-Rich Domain Impair Its S100A6-Mediated Fibril Dissolution.ACS chemical neuroscience · 2023Article
- Studying micro to millisecond protein dynamics using simple amideJournal of biomolecular NMR · 2023Article
- Reversible phase separation of ESCRT protein ALIX through tyrosine phosphorylation.Science advances · 2023Article
- The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations.Computational and structural biotechnology journal · 2021Article
- Article
- Probing the Interaction between HIV-1 Protease and the Homodimeric p66/p66' Reverse Transcriptase Precursor by Double Electron-Electron Resonance EPR Spectroscopy.Chembiochem : a European journal of chemical biology · 2020Article
- Proline-rich domain of human ALIX contains multiple TSG101-UEV interaction sites and forms phosphorylation-mediated reversible amyloids.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Picomolar to Micromolar: Elucidating the Role of Distal Mutations in HIV-1 Protease in Conferring Drug Resistance.ACS chemical biology · 2019Article
- Inhibition of HIV Maturation via Selective Unfolding and Cross-Linking of Gag Polyprotein by a Mercaptobenzamide Acetylator.Journal of the American Chemical Society · 2019Article
- Binding kinetics and substrate selectivity in HIV-1 protease-Gag interactions probed at atomic resolution by chemical exchange NMR.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Gp41 and Gag amino acids linked to HIV-1 protease inhibitor-based second-line failure in HIV-1 subtype A from Western Kenya.Journal of the International AIDS Society · 2017Article
- Evolution of gag and gp41 in Patients Receiving Ritonavir-Boosted Protease Inhibitors.Scientific reports · 2017Article
- Gag-protease coevolution analyses define novel structural surfaces in the HIV-1 matrix and capsid involved in resistance to Protease Inhibitors.Scientific reports · 2017Article
- Probing conformational dynamics in biomolecules via chemical exchange saturation transfer: a primer.Journal of biomolecular NMR · 2017Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Cleavage of the group-specific antigen (Gag) polyprotein by HIV-1 protease represents the critical first step in the conversion of immature noninfectious viral particles to mature infectious virions. Selective pressure exerted by HIV-1 protease inhibitors, a mainstay of current anti-HIV-1 therapies, results in the accumulation of drug resistance mutations in both protease and Gag. Surprisingly, a large number of these mutations (known as secondary or compensatory mutations) occur outside the active site of protease or the cleavage sites of Gag (located within intrinsically disordered linkers connecting the globular domains of Gag to one another), suggesting that transient encounter complexes involving the globular domains of Gag may play a role in guiding and facilitating access of the protease to the Gag cleavage sites. Here, using large fragments of Gag, as well as catalytically inactive and active variants of protease, we probe the nature of such rare encounter complexes using intermolecular paramagnetic relaxation enhancement, a highly sensitive technique for detecting sparsely populated states. We show that Gag-protease encounter complexes are primarily mediated by interactions between protease and the globular domains of Gag and that the sites of transient interactions are correlated with surface exposed regions that exhibit a high propensity to mutate in the presence of HIV-1 protease inhibitors.
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