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.
Department of Chemistry, Indiana University, Bloomington, IN 47405-0001, USA.
Michael R
MR
Mayer
Todd R
TR
Parody
Amita
A
Datta-Mannan
Martin J
MJ
Stone
D000595:Amino Acid Sequence; D001665:Binding Sites; D054413:Chemokine CCL11; D018932:Chemokine CCL2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018925:Chemokines / Q000494:pharmacology; D019742:Chemokines, CC / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D019707:Receptors, Chemokine / Q000187:drug effects / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012680:Sensitivity and Specificity
D054413:Chemokine CCL11; D018932:Chemokine CCL2; D018925:Chemokines; D019742:Chemokines, CC; D019707:Receptors, Chemokine; D011993:Recombinant Fusion Proteins