{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kleist AB"],"funding":["NIAID NIH HHS","NHLBI NIH HHS","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["3603-3622.e27"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12435897"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["188(13)"],"pubmed_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"],"pubmed_title":["Encoding and decoding selectivity and promiscuity in the human chemokine-GPCR interaction network."],"pmcid":["PMC12435897"],"funding_grant_id":["F30 CA236182","K99 CA240689","R37 AI058072","F30 HL134253","T32 GM080202","R35 GM137836","F30 CA196040"],"pubmed_authors":["Slodkowicz G","Wedemeyer MJ","McGrail DJ","Talbot LJ","Yi SS","Dishman AF","Sluter M","Crawford KS","Peterson FC","Chevigne A","Kleist AB","Malinverni D","Babu MM","Szpakowska M","Volkman BF","Sahni N","Thomas MA"],"additional_accession":[]},"is_claimable":false,"name":"Encoding and decoding selectivity and promiscuity in the human chemokine-GPCR interaction network.","description":"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.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jun","modification":"2026-06-03T03:00:15.937Z","creation":"2026-04-23T03:13:28.88Z"},"accession":"S-EPMC12435897","cross_references":{"pubmed":["40273912"],"doi":["10.1016/j.cell.2025.03.046"]}}