Dimer dissociation is essential for interleukin-8 (IL-8) binding to CXCR1 receptor

Harshica Fernando, Christopher Chin, Jörg Rösgen, Krishna Rajarathnam

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Chemokines play a fundamental role in trafficking of immune cells and in host defense against infection. The role of chemokines in the recruitment process is highly regulated spatially and temporally and involves interactions with G protein-coupled receptors and cell surface glycosaminoglycans. The dynamic equilibrium between chemokine monomers and dimers, both free in solution and in cell surface-bound forms, regulates different components of recruitment such as chemotaxis and receptor signaling. The binding and activity of the chemokine interleukin-8 (IL-8) for its receptors, previously studied using "trapped" non-associating monomers and non-dissociating dimers, show that the monomer has a native-like function but support conflicting roles for the dinner. We have measured the binding of native IL-8 to the CXCR1 N-domain, using isothermal titration calorimetry and sedimentation equilibrium techniques. The N-domain constitutes a critical binding site, and IL-8 binding affinity to the receptor N-domain is in the same concentration range as the IL-8 monomer-dimer equilibrium. We observed that only the IL-8 monomer, and not the dimer, is competent in binding the receptor N-domain. Based on our results, we propose that IL-8 dinterization functions as a negative regulator for the receptor function and as a positive regulator for binding to glycosaminoglycans and that both play a role in the neutrophil recruitment process.

Original languageEnglish (US)
Pages (from-to)36175-36178
Number of pages4
JournalJournal of Biological Chemistry
Volume279
Issue number35
DOIs
StatePublished - Aug 27 2004

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Interleukin-8A Receptors
Interleukin-8
Dimers
Chemokines
Monomers
Glycosaminoglycans
Interleukin-8 Receptors
Calorimetry
Neutrophil Infiltration
Chemotaxis
G-Protein-Coupled Receptors
Titration
Sedimentation
Meals
Binding Sites
Infection

ASJC Scopus subject areas

  • Biochemistry

Cite this

Dimer dissociation is essential for interleukin-8 (IL-8) binding to CXCR1 receptor. / Fernando, Harshica; Chin, Christopher; Rösgen, Jörg; Rajarathnam, Krishna.

In: Journal of Biological Chemistry, Vol. 279, No. 35, 27.08.2004, p. 36175-36178.

Research output: Contribution to journalArticle

Fernando, Harshica ; Chin, Christopher ; Rösgen, Jörg ; Rajarathnam, Krishna. / Dimer dissociation is essential for interleukin-8 (IL-8) binding to CXCR1 receptor. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 35. pp. 36175-36178.
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