Mechanisms of chemokine recognition and receptor activation of chemokine receptor CCR7
Bibliographic record
Abstract
The chemokine receptor C-C chemokine receptor (CCR7) is essential for immune cell trafficking, cancer metastasis, and autoimmune diseases, making it a significant therapeutic target. This study presents cryo-electron microscopy (cryo-EM) structures of CCR7-G i complexes bound to CCL19 and CCL21, revealing detailed interactions between the receptor, the two chemokines, and the Gα i protein. Key N-terminal residues and a conserved aromatic patch in the orthosteric pocket are crucial for receptor activation by both ligands, with CCL19 also establishing additional polar interactions that are critical for this process. Mutagenesis studies demonstrate that mutations in these residues result in variable effects on ligand-induced activation, emphasizing the distinct interaction modes of CCL19 and CCL21 with CCR7. Notably, we identify an interesting activation mechanism for CCR7, in which the conventional toggle switch residue W 6.48 is replaced by Q 6.48 , leading to distinctive conformational changes upon ligand binding. These insights enhance our understanding of G-protein-coupled receptor (GPCR) signaling diversity and lay the groundwork for future therapeutic interventions targeting CCR7.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".