ArticleCellular and molecular life sciences : CMLS2021
The C-terminal peptide of CCL21 drastically augments CCL21 activity through the dendritic cell lymph node homing receptor CCR7 by interaction with the receptor N-terminus.
Article in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Spatial profiling uncovers multicellular dynamics in early relapse of hepatitis B virus-associated follicular lymphoma.Communications biology · 2026Article
- An Exploratory Study of the Impact of a CCL21-Derived C-Terminal Peptide on Dendritic Cell Lymph Node Homing.Journal of immunology research · 2026Article
- G-Protein-Coupled Receptor Kinase 2 Limits CCL21-Induced T Cell Migration via Phospholipase Cγ1.Receptors (Basel, Switzerland) · 2025Article
- Decoding the immune landscape in Ewing sarcoma pathogenesis: The role of tumor infiltrating immune cells and immune milieu.Journal of bone oncology · 2025Review
- GPR15LG binds CXCR4 and synergistically modulates CXCL12-induced cell signaling and migration.Cell communication and signaling : CCS · 2025Article
- Molecular and Cellular Machinery of Lymphatic Metastasis in Breast Cancer.OncoTargets and therapy · 2025Review
- Chemokines in the resolution of inflammation: key players and targets for therapeutic modulation.Frontiers in immunology · 2025Review
- The Biology of Dendritic Cells: In Health and Disease.Advances in experimental medicine and biology · 2025Review
- Chemokine Receptor N-Terminus Charge Dictates Reliance on Post-Translational Modifications for Effective Ligand Capture and Following Boosting by Defense Peptides.International journal of molecular sciences · 2024Article
- Systematic Assessment of Human CCR7 Signalling Using NanoBRET Biosensors Points towards the Importance of the Cellular Context.Biosensors · 2024Article
- Role of tertiary lymphoid structures and B cells in clinical immunotherapy of gastric cancer.Frontiers in immunology · 2024Review
- Chemokine binding to PSGL-1 is controlled by O-glycosylation and tyrosine sulfation.Cell chemical biology · 2023Article
- "Glyco-sulfo barcodes" regulate chemokine receptor function.Cellular and molecular life sciences : CMLS · 2023Article
- Heparin Specifically Interacts with Basic BBXB Motifs of the Chemokine CCL21 to Define CCR7 Signaling.International journal of molecular sciences · 2023Article
- Physiology of chemokines in the cancer microenvironment.American journal of physiology. Cell physiology · 2023Review
- Rewiring host-microbe interactions and barrier function during gastrointestinal inflammation.Gastroenterology report · 2022Review
- Selective Boosting of CCR7-Acting Chemokines; Short Peptides Boost Chemokines with Short Basic Tails, Longer Peptides Boost Chemokines with Long Basic Tails.International journal of molecular sciences · 2022Article
- The Multi-Functional Roles of CCR7 in Human Immunology and as a Promising Therapeutic Target for Cancer Therapeutics.Frontiers in molecular biosciences · 2022Review
- Affinity and Specificity for Binding to Glycosaminoglycans Can Be Tuned by Adapting Peptide Length and Sequence.International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
The endogenous chemokines CCL19 and CCL21 signal via their common receptor CCR7. CCL21 is the main lymph node homing chemokine, but a weak chemo-attractant compared to CCL19. Here we show that the 41-amino acid positively charged peptide, released through C-terminal cleavage of CCL21, C21TP, boosts the immune cell recruiting activity of CCL21 by up to 25-fold and the signaling activity via CCR7 by ~ 100-fold. Such boosting is unprecedented. Despite the presence of multiple basic glycosaminoglycan (GAG) binding motifs, C21TP boosting of CCL21 signaling does not involve interference with GAG mediated cell-surface retention. Instead, boosting is directly dependent on O-glycosylations in the CCR7 N-terminus. As dictated by the two-step binding model, the initial chemokine binding involves interaction of the chemokine fold with the receptor N-terminus, followed by insertion of the chemokine N-terminus deep into the receptor binding pocket. Our data suggest that apart from a role in initial chemokine binding, the receptor N-terminus also partakes in a gating mechanism, which could give rise to a reduced ligand activity, presumably through affecting the ligand positioning. Based on experiments that support a direct interaction of C21TP with the glycosylated CCR7 N-terminus, we propose that electrostatic interactions between the positively charged peptide and sialylated O-glycans in CCR7 N-terminus may create a more accessible version of the receptor and thus guide chemokine docking to generate a more favorable chemokine-receptor interaction, giving rise to the peptide boosting effect.
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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.