ArticleThe Journal of biological chemistry2012
Peptides from second extracellular loop of C-C chemokine receptor type 5 (CCR5) inhibit diverse strains of HIV-1.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Impedimetric antimicrobial peptide biosensor for the detection of human immunodeficiency virus envelope protein gp120.iScience · 2024Article
- Peptide-Based HIV Entry Inhibitors.Advances in experimental medicine and biology · 2022Article
- Virus Entry Inhibitors: Past, Present, and Future.Advances in experimental medicine and biology · 2022Review
- Peptides to combat viral infectious diseases.Peptides · 2020Review
- Discoveries and developments of CXCR4-targeted HIV-1 entry inhibitors.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- Article
- Design of HIV Coreceptor Derived Peptides That Inhibit Viral Entry at Submicromolar Concentrations.Molecular pharmaceutics · 2017Article
- The Membrane-Proximal Region of C-C Chemokine Receptor Type 5 Participates in the Infection of HIV-1.Frontiers in immunology · 2017Article
- The Role of Natural Antibodies to CC Chemokine Receptor 5 in HIV Infection.Frontiers in immunology · 2017Review
- The C4 region as a target for HIV entry inhibitors--NMR mapping of the interacting segments of T20 and gp120.The FEBS journal · 2015Article
- Investigation of Inhibition Mechanism of Chemokine Receptor CCR5 by Micro-second Molecular Dynamics Simulations.Scientific reports · 2015Article
- HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth.Expert opinion on therapeutic targets · 2015Review
- An extended CCR5 ECL2 peptide forms a helix that binds HIV-1 gp120 through non-specific hydrophobic interactions.The FEBS journal · 2015Article
- Protein and oligonucleotide delivery systems for vaginal microbicides against viral STIs.Cellular and molecular life sciences : CMLS · 2015Review
- Investigation of interactions at the extracellular loops of the relaxin family peptide receptor 1 (RXFP1).The Journal of biological chemistry · 2014Article
- Allosteric and biased g protein-coupled receptor signaling regulation: potentials for new therapeutics.Frontiers in endocrinology · 2014Review
- Article
- Linking genotype to phenotype on beads: high throughput selection of peptides with biological function.Scientific reports · 2013Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
To initiate HIV entry, the HIV envelope protein gp120 must engage its primary receptor CD4 and a coreceptor CCR5 or CXCR4. In the absence of a high resolution structure of a gp120-coreceptor complex, biochemical studies of CCR5 have revealed the importance of its N terminus and second extracellular loop (ECL2) in binding gp120 and mediating viral entry. Using a panel of synthetic CCR5 ECL2-derived peptides, we show that the C-terminal portion of ECL2 (2C, comprising amino acids Cys-178 to Lys-191) inhibit HIV-1 entry of both CCR5- and CXCR4-using isolates at low micromolar concentrations. In functional viral assays, these peptides inhibited HIV-1 entry in a CD4-independent manner. Neutralization assays designed to measure the effects of CCR5 ECL2 peptides when combined with either with the small molecule CD4 mimetic NBD-556, soluble CD4, or the CCR5 N terminus showed additive inhibition for each, indicating that ECL2 binds gp120 at a site distinct from that of N terminus and acts independently of CD4. Using saturation transfer difference NMR, we determined the region of CCR5 ECL2 used for binding gp120, showed that it can bind to gp120 from both R5 and X4 isolates, and demonstrated that the peptide interacts with a CD4-gp120 complex in a similar manner as to gp120 alone. As the CCR5 N terminus-gp120 interactions are dependent on CD4 activation, our data suggest that gp120 has separate binding sites for the CCR5 N terminus and ECL2, the ECL2 binding site is present prior to CD4 engagement, and it is conserved across CCR5- and CXCR4-using strains. These peptides may serve as a starting point for the design of inhibitors with broad spectrum anti-HIV activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.