Solution structure of eotaxin, a chemokine that selectively recruits eosinophils in allergic inflammation

92Citations
Citations of this article
37Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

The solution structure of the CCR3-specific chemokine, eotaxin, has been determined by NMR spectroscopy. The quaternary structure of eotaxin was investigated by ultracentrifugation and NMR, and it was found to be in equilibrium between monomer and dimer under a wide range of conditions. At pH ≤ 5 and low ionic strength, eotaxin was found to be predominantly a monomer. The three-dimensional structure of the eotaxin monomer solved at pH 5.0 revealed that it has a typical chemokine fold, which includes a 3-stranded β-sheet and an overlying α-helix. Except for the N-terminal residues (residues 1-8), the core of the protein is well defined. The eotaxin structure is compared with the chemokines regulated upon activation, normal T-cell expressed and secreted (RANTES) and monocyte chemoattractant protein- 1 (MCP-1); eotaxin binds only CC chemokine receptor CCR3, whereas RANTES binds many receptors including CCR3, and MCP-1 binds a distinct receptor, CCR2. The RMSD of the eotaxin ensemble of structures with the RANTES average minimized monomeric subunit is 5.52 ± 0.87 Å over all backbone atoms and 1.14 ± 0.09 Å over backbone atoms of residues 11-28 and 34-65. The most important difference between the structures is in the N-terminal residues that are unstructured in eotaxin but structured in RANTES and MCP-1. Several residues in the loop region of RANTES show similar packing in eotaxin (residues 11-17). As the N-terminal and loop regions have been shown to be critical for receptor binding and signaling, this structure will be useful for determining the basis for CCR3 selectivity of the eotaxin.

Cite

CITATION STYLE

APA

Crump, M. P., Rajarathnam, K., Kim, K. S., Clark-Lewis, I., & Sykes, B. D. (1998). Solution structure of eotaxin, a chemokine that selectively recruits eosinophils in allergic inflammation. Journal of Biological Chemistry, 273(35), 22471–22479. https://doi.org/10.1074/jbc.273.35.22471

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free