{"doi":"10.1016/j.cell.2025.03.046","title":"Encoding and decoding selectivity and promiscuity in the human chemokine-GPCR interaction network","abstract":"In humans, selective and promiscuous interactions between 46 secreted chemokine ligands and 23 cell surface chemokine receptors of the G-protein-coupled receptor (GPCR) family form a complex network to coordinate cell migration. While chemokines and their GPCRs each share common structural scaffolds, the molecular principles driving selectivity and promiscuity remain elusive. Here, we identify conserved, semi-conserved, and variable determinants (i.e., recognition elements) that are encoded and decoded by chemokines and their receptors to mediate interactions. Selectivity and promiscuity emerge from an ensemble of generalized (\"public/conserved\") and specific (\"private/variable\") determinants distributed among structured and unstructured protein regions, with ligands and receptors recognizing these determinants combinatorially. We employ these principles to engineer a viral chemokine with altered GPCR coupling preferences and provide a web resource to facilitate sequence-structure-function studies and protein design efforts for developing immuno-therapeutics and cell therapies.","journal":"Cell","year":2025,"id":513777,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9443,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":442133,"name":"Martyna Szpakowska","orcid":"0000-0002-5659-8377","position":1,"is_corresponding":false},{"id":696359,"name":"Lindsay J. Talbot","orcid":"0000-0001-7409-9873","position":2,"is_corresponding":false},{"id":268962,"name":"Greg Slodkowicz","orcid":null,"position":3,"is_corresponding":false},{"id":262329,"name":"Duccio Malinverni","orcid":"0000-0002-3946-9709","position":4,"is_corresponding":false},{"id":439420,"name":"Monica A. Thomas","orcid":"0000-0003-2513-3371","position":5,"is_corresponding":false},{"id":369822,"name":"Kyler Crawford","orcid":"0000-0002-9281-791X","position":6,"is_corresponding":false},{"id":268272,"name":"Daniel J. McGrail","orcid":"0000-0002-6669-6069","position":7,"is_corresponding":false},{"id":275179,"name":"Acacia F. Dishman","orcid":"0000-0002-8952-8551","position":8,"is_corresponding":false},{"id":369820,"name":"Michael J. Wedemeyer","orcid":"0000-0003-2213-0896","position":9,"is_corresponding":false},{"id":338275,"name":"Madison N. Sluter","orcid":null,"position":10,"is_corresponding":false},{"id":56383,"name":"S. Stephen Yi","orcid":"0000-0003-0047-8103","position":11,"is_corresponding":false},{"id":56377,"name":"Nidhi Sahni","orcid":"0000-0002-9155-5882","position":12,"is_corresponding":false},{"id":275184,"name":"Francis C. Peterson","orcid":"0000-0001-9890-4224","position":13,"is_corresponding":false},{"id":1375562,"name":"Andy Chevigné","orcid":"0000-0002-8089-6665","position":14,"is_corresponding":false},{"id":275185,"name":"Brian F. Volkman","orcid":"0000-0002-6681-5179","position":15,"is_corresponding":false},{"id":91395,"name":"M. Madan Babu","orcid":"0000-0003-0556-6196","position":16,"is_corresponding":false},{"id":275182,"name":"Andrew B. Kleist","orcid":"0000-0002-4954-010X","position":0,"is_corresponding":true}],"reference_count":138,"raw_metadata":null,"created_at":"2026-07-19T02:48:23.284782Z","pmid":"40273912","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}