NMR Solution Structure and Backbone Dynamics of the CC Chemokine Eotaxin-3,

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Abstract
Eotaxin-3 is one of three related chemokines that specifically activate chemokine receptor CCR3. We report the 3D structure and backbone dynamics of eotaxin-3 determined by NMR spectroscopy. Eotaxin-3 is monomeric under the conditions in this study and consists of an unstructured N-terminus before the first two conserved cysteine residues, an irregularly structured N-loop following the second conserved cysteine, a single turn of 310-helix, a three-stranded antiparallel β-sheet, an α-helix, and an unstructured C-terminal tail. As in other chemokines, the α-helix packs against one face of the β-sheet. The average backbone and heavy atom rmsd values of the 20 structures (residues 9−65) are 0.44 and 1.01 Å, respectively. A comparison between the structures of eotaxin-3 and related chemokines suggests that the electrostatic potential in the vicinity of a surface groove and the structure of the β2−β3 turn may be important for maintaining receptor specificity. The backbone dynamics of eotaxin-3 were determined from 15N NMR relaxation data using the extended model free dynamics formalism. Large amplitude motions on the picosecond to nanosecond time scale were observed in both termini and in some residues in the N-loop, the β1−β2 turn, and the β3 strand; the location of these residues suggests a possible role for dynamics in receptor binding and activation. In contrast to eotaxin, eotaxin-3 exhibits no substantial mobility on the microsecond to millisecond time scale.