ArticleNature communications2025
Noncanonical roles of chemokine regions in CCR9 activation revealed by structural modeling and mutational mapping.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed.
- Polymeric Materials in Cancer Immunotherapy: Advances, Challenges, and Future Directions.Polymer science & technology (Washington, D.C.) · 2026Review
- Elevated conformational dynamics makes ACKR3 activation-prone and G protein-incompetent.bioRxiv : the preprint server for biology · 2026Article
- Modulation of Chemokine Activity for Enhanced Angiogenesis and Tissue Regeneration in Chronic Wounds.International journal of molecular sciences · 2026Review
- Signaling bias of the protease-activated receptor-1 is dictated by distinct GRK5 and β-arrestin-2 determinants.Cell reports · 2026Article
- Atypical GPCR Activation Resolved by Nanobody Engineering.bioRxiv : the preprint server for biology · 2026Article
- Rules of engagement: Determinants of chemokine receptor activation and selectivity by CCL27 and CCL28.The Journal of biological chemistry · 2025Article
- AI meets physics in computational structure-based drug discovery for GPCRs.npj drug discovery · 2025Review
- Essential strategies for the detection of constitutive and ligand-dependent Gi-directed activity of 7TM receptors using bioluminescence resonance energy transfer.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
The G protein-coupled chemokine receptor CCR9 plays a major role in inflammatory bowel disease and is implicated in cancer. Despite its therapeutic relevance, the mechanism by which CCR9 is activated by its endogenous chemokine CCL25 remains poorly understood. Here, we combine structural modeling with multimodal pharmacological analysis of CCR9 mutants to map the CCR9-CCL25 interface and delineate key determinants of binding, G protein versus arrestin signaling, and constitutive activity. We show that unlike other chemokines which drive receptor activation through their N-termini, CCL25 activates CCR9 via a distinct region, its 30s loop. Supporting this non-canonical mechanism, CCR9 signaling tolerates alanine mutations in the CCL25 N-terminus but is strongly affected by 30s loop modifications. Engineered N-terminally modified CCL25 analogs remain full agonists, consistent with signaling determinants lying outside the N-terminus. This non-canonical activation signature provides insights for CCR9 drug discovery and may inform structure-based design for other chemokine receptors.
Indexed as
Identifiers
What OpenQuestion holds
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.