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http://purl.uniprot.org/citations/10368283http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10368283http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/10368283http://www.w3.org/2000/01/rdf-schema#comment"

Background

Interactions between CXC chemokines (e.g. interleukin-8, IL-8) and their receptors (e.g. CXCR-1) have a key role in host defense and disease by attracting and upregulating neutrophils to sites of inflammation. The transmembrane nature of the receptor impedes structure-based understanding of ligand interactions. Linear peptides based on the N-terminal, extracellular portion of the receptor CXCR-1 do bind to IL-8, however, and inhibit the binding of IL-8 to the full-length receptor.

Results

The NMR solution structure of the complex formed between IL-8 and one such receptor-based peptide indicates that a cleft between a loop and a beta hairpin constitute part of the receptor interaction surface on IL-8. Nine residues from the C terminus of the receptor peptide (corresponding to Pro21-Pro29 of CXCR-1) occupy the cleft in an extended fashion. Intermolecular contacts are mostly hydrophobic and sidechain mediated.

Conclusions

The results offer the first details at an atomic level of the interaction between a chemokine and its receptor. Consideration of other biochemical data allow extrapolation to a model for the interaction of IL-8 with the full-length receptor. In this model, the heparin-binding residues of IL-8 are exposed, thereby allowing presentation of the chemokine from endothelial cell-surface glycosaminoglycans. This first glimpse of how IL-8 binds to its receptor provides a foundation for the structure-based design of chemokine antagonists."xsd:string
http://purl.uniprot.org/citations/10368283http://purl.org/dc/terms/identifier"doi:10.1016/s0969-2126(99)80022-7"xsd:string
http://purl.uniprot.org/citations/10368283http://purl.org/dc/terms/identifier"doi:10.1016/s0969-2126(99)80022-7"xsd:string
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/author"Reilly D."xsd:string
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/author"Reilly D."xsd:string
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/author"Skelton N.J."xsd:string
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/author"Skelton N.J."xsd:string
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/author"Quan C."xsd:string
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/author"Quan C."xsd:string
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/author"Lowman H."xsd:string
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/author"Lowman H."xsd:string
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/date"1999"xsd:gYear
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/date"1999"xsd:gYear
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/name"Structure"xsd:string
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/name"Structure"xsd:string
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/pages"157-168"xsd:string
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/pages"157-168"xsd:string
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/title"Structure of a CXC chemokine-receptor fragment in complex with interleukin-8."xsd:string
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/title"Structure of a CXC chemokine-receptor fragment in complex with interleukin-8."xsd:string
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/volume"7"xsd:string
http://purl.uniprot.org/citations/10368283http://purl.uniprot.org/core/volume"7"xsd:string
http://purl.uniprot.org/citations/10368283http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/10368283
http://purl.uniprot.org/citations/10368283http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/10368283
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