2eot

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Template:STRUCTURE 2eot

SOLUTION STRUCTURE OF EOTAXIN, AN ENSEMBLE OF 32 NMR SOLUTION STRUCTURES


Overview

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 beta-sheet and an overlying alpha-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 A over all backbone atoms and 1.14 +/- 0.09 A 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.

About this Structure

2EOT is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Solution structure of eotaxin, a chemokine that selectively recruits eosinophils in allergic inflammation., Crump MP, Rajarathnam K, Kim KS, Clark-Lewis I, Sykes BD, J Biol Chem. 1998 Aug 28;273(35):22471-9. PMID:9712872 Page seeded by OCA on Sun May 4 02:54:41 2008

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