Backbone dynamics of the CC-chemokine eotaxin-2 and comparison among the eotaxin group chemokines

The eotaxin group chemokines (eotaxin, eotaxin-2, and eotaxin-3) share only 35-41% sequence identity but are all agonists for the receptor CCR3. Here we present a detailed comparison between the backbone dynamics of these three chemokines. The dynamics of eotaxin-2 were determined from 15N NMR relaxation data and compared to those obtained previously for eotaxin and eotaxin-3. For all three chemokines, the majority of residues in the first two beta-strands and the alpha-helix show highly restricted motions on the subnanosecond time scale but there is dramatically higher flexibility in the N- and C-terminal regions and also substantial mobility for residues in the N-loop region and the third beta-strand. The latter two regions form a groove on the chemokine surface that is the likely binding site for the N-terminal region of the receptor. Taken together, the available data suggest a model in which conformational rearrangements of both the chemokine and the receptor are likely to occur during binding and receptor activation.