Structure of a CXC chemokine-receptor fragment in complex with interleukin-8

Structure. 1999 Feb 15;7(2):157-68. doi: 10.1016/S0969-2126(99)80022-7.


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.

MeSH terms

  • Amino Acid Sequence
  • Antigens, CD / chemistry*
  • Glycosaminoglycans / metabolism
  • Interleukin-8 / chemistry*
  • Magnetic Resonance Spectroscopy
  • Membrane Proteins / chemistry
  • Models, Molecular
  • Molecular Conformation
  • Molecular Sequence Data
  • Neutrophils / metabolism
  • Peptide Fragments / chemistry
  • Protein Binding
  • Protein Conformation*
  • Protein Structure, Secondary
  • Receptors, Interleukin / chemistry*
  • Receptors, Interleukin-8A


  • Antigens, CD
  • Glycosaminoglycans
  • Interleukin-8
  • Membrane Proteins
  • Peptide Fragments
  • Receptors, Interleukin
  • Receptors, Interleukin-8A

Associated data

  • PDB/1ILP
  • PDB/1ILQ