1ilp: Difference between revisions
New page: left|200px<br /> <applet load="1ilp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ilp" /> '''CXCR-1 N-TERMINAL PEPTIDE BOUND TO INTERLEU... |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:1ilp.gif|left|200px]]<br /> | [[Image:1ilp.gif|left|200px]]<br /><applet load="1ilp" size="350" color="white" frame="true" align="right" spinBox="true" | ||
<applet load="1ilp" size=" | |||
caption="1ilp" /> | caption="1ilp" /> | ||
'''CXCR-1 N-TERMINAL PEPTIDE BOUND TO INTERLEUKIN-8'''<br /> | '''CXCR-1 N-TERMINAL PEPTIDE BOUND TO INTERLEUKIN-8'''<br /> | ||
==Overview== | ==Overview== | ||
BACKGROUND: Interactions between CXC chemokines (e.g. interleukin-8, IL-8) | 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. | ||
==Disease== | ==Disease== | ||
| Line 11: | Line 10: | ||
==About this Structure== | ==About this Structure== | ||
1ILP is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ACE and NH2 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | 1ILP is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ACE:'>ACE</scene> and <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ILP OCA]. | ||
==Reference== | ==Reference== | ||
| Line 19: | Line 18: | ||
[[Category: Lowman, H.]] | [[Category: Lowman, H.]] | ||
[[Category: Quan, C.]] | [[Category: Quan, C.]] | ||
[[Category: Skelton, N | [[Category: Skelton, N J.]] | ||
[[Category: ACE]] | [[Category: ACE]] | ||
[[Category: NH2]] | [[Category: NH2]] | ||
[[Category: cytokine]] | [[Category: cytokine]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:13:07 2008'' | ||
Revision as of 14:13, 21 February 2008
|
CXCR-1 N-TERMINAL PEPTIDE BOUND TO INTERLEUKIN-8
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: AIDS, slow progression to OMIM:[146929]
About this StructureAbout this Structure
1ILP is a Protein complex structure of sequences from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Structure of a CXC chemokine-receptor fragment in complex with interleukin-8., Skelton NJ, Quan C, Reilly D, Lowman H, Structure. 1999 Feb 15;7(2):157-68. PMID:10368283
Page seeded by OCA on Thu Feb 21 13:13:07 2008