PDBsum entry: 1ilq

Cytokine

PDB id: 1ilq

Contents

Protein chains

71 a.a. *

19 a.a. *

* Residue conservation analysis

PDB id:

1ilq

Name:

Cytokine

Title:

Cxcr-1 n-terminal peptide bound to interleukin-8 (minimized mean)

Structure:

Interleukin-8 precursor. Chain: a, b. Synonym: il-8. Engineered: yes. Interleukin-8 receptor a. Chain: c. Fragment: 9-29. Synonym: il8-ra. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli k12. Expression_system_taxid: 83333. (Pphoa). Organism_taxid: 9606

NMR struc:

1 models

Authors:

N.J.Skelton,C.Quan,H.Lowman

Key ref:

N.J.Skelton et al. (1999). Structure of a CXC chemokine-receptor fragment in complex with interleukin-8. Structure, 7, 157-168. PubMed id: 10368283 DOI: 10.1016/S0969-2126(99)80022-7

Date:

17-Dec-98 Release date: 23-Dec-98

Protein chains

P10145  (IL8_HUMAN) -  Interleukin-8

Seq: 99 a.a.

Struc: 71 a.a.

Protein chain

P25024  (CXCR1_HUMAN) -  C-X-C chemokine receptor type 1

Seq: 350 a.a.

Struc: 18 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

 Gene Ontology (GO) functional annotation 

• Cellular component: extracellular region (3 terms)
• Biological process: intracellular signal transduction (21 terms)
• Biochemical function: protein binding (4 terms)

DOI no: 10.1016/S0969-2126(99)80022-7

Structure 7:157-168 (1999)

PubMed id: 10368283

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

N.J.Skelton, C.Quan, D.Reilly, H.Lowman.

ABSTRACT

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.

Selected figure(s)

Figure 7.
Figure 7. Model for the presentation of IL-8 by endothelial cell-surface glycosaminoglycans to the CXCR-1 receptor on a passing neutrophil. The structural details from the present manuscript are shown with purple (IL-8) and blue (CXCR1-p1) tubes. CXCR-1 is shown schematically in blue, with the ELR sequence of IL-8 (in yellow) pointing towards extracellular loops 3 and 4 of the receptor. The basic residues of IL-8 that interact with heparin fragments (dark purple) [37] , are shown interacting with a schematic glycosaminoglycan (black) on the endothelial surface.

The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 157-168) copyright 1999.

Figure was selected by the author.