Specificity determinants for chemokine recognition identified using eotaxin-MCP-1 chimeras

To identify the elements of two chemokines [monocyte chemoattractant protein-1 (MCP-1) and eotaxin] that control their differential recognition by their respective receptors (CCR2 and CCR3), we have studied the receptor interactions of MCP-1-eotaxin chimeras. Each receptor was found to exhibit a distinct binding preference for proteins containing the amino-terminal region of the cognate chemokine for that receptor. However, other elements dictating chemokine preference were different for the two receptors. In some cases, the influence of replacing a particular region was dependent on the identities of neighboring regions, indicating a complex network of cooperative and/or compensating interactions.