ArticleACS chemical biology2015
Engineering Metamorphic Chemokine Lymphotactin/XCL1 into the GAG-Binding, HIV-Inhibitory Dimer Conformation.
Article in ACS chemical biology, 2015. 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.
The trial behind it
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.
- The multifaceted role of XCL1 in health and disease.Protein science : a publication of the Protein Society · 2025Review
- Design and discovery of metamorphic proteins.Current opinion in structural biology · 2022Review
- Metamorphic proteins under a computational microscope: Lessons from a fold-switching RfaH protein.Computational and structural biotechnology journal · 2022Review
- Specific binding-induced modulation of the XCL1 metamorphic equilibrium.Biopolymers · 2021Article
- Metamorphic Protein Folding Encodes Multiple Anti-Pathogens (Basel, Switzerland) · 2021Article
- Metamorphic proteins: the Janus proteins of structural biology.Open biology · 2021Article
- Gill transcriptomes reveal expression changes of genes related with immune and ion transport under salinity stress in silvery pomfret (Pampus argenteus).Fish physiology and biochemistry · 2020Article
- Switchable Membrane Remodeling and Antifungal Defense by Metamorphic Chemokine XCL1.ACS infectious diseases · 2020Article
- Targeting Chemokine-Glycosaminoglycan Interactions to Inhibit Inflammation.Frontiers in immunology · 2020Review
- Structure-function guided modeling of chemokine-GPCR specificity for the chemokine XCL1 and its receptor XCR1.Science signaling · 2019Article
- Unfolding the Mysteries of Protein Metamorphosis.ACS chemical biology · 2018Review
- Cytokines Elevated in HIV Elite Controllers Reduce HIV ReplicationJournal of virology · 2017Article
- Mechanisms of Regulation of the Chemokine-Receptor Network.International journal of molecular sciences · 2017Review
- Depot-specific inflammation with decreased expression of ATM2 in white adipose tissues induced by high-margarine/lard intake.PloS one · 2017Article
- Chemokines and their receptors: insights from molecular modeling and crystallography.Current opinion in pharmacology · 2016Review
- Transferring the C-terminus of the chemokine CCL21 to CCL19 confers enhanced heparin binding.Biochemical and biophysical research communications · 2016Article
- New paradigms in chemokine receptor signal transduction: Moving beyond the two-site model.Biochemical pharmacology · 2016Review
- A Requirement for Metamorphic Interconversion in the Antimicrobial Activity of Chemokine XCL1.Biochemistry · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Unlike other chemokines, XCL1 undergoes a distinct metamorphic interconversion between a canonical monomeric chemokine fold and a unique β-sandwich dimer. The monomeric conformation binds and activates the receptor XCR1, whereas the dimer binds extracellular matrix glycosaminoglycans and has been associated with anti-human immunodeficiency virus (HIV) activity. Functional studies of WT-XCL1 are complex, as both conformations are populated in solution. To overcome this limitation, we engineered a stabilized dimeric variant of XCL1 designated CC5. This variant features a new disulfide bond (A36C-A49C) that prevents structural interconversion by locking the chemokine into the β-sandwich dimeric conformation, as demonstrated by NMR structural analysis and hydrogen/deuterium exchange experiments. Functional studies analyzing glycosaminoglycan binding demonstrate that CC5 binds with high affinity to heparin. In addition, CC5 exhibits potent inhibition of HIV-1 activity in primary peripheral blood mononuclear cells (PBMCs), demonstrating the importance of the dimer in blocking viral infection. Conformational variants like CC5 are valuable tools for elucidating the biological relevance of the XCL1 native-state interconversion and will assist in future antiviral and functional studies.
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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.